臺灣博碩士論文加值系統

Contents

Application for Embargo of Thesis i
Signature Page ii
Thesis Approval Form iii
Acknowledgments iv
Chinese Abstract v
English Abstract vi
Table of Contents vii
List of Figures ix
List of Tables xi
Chapter 1 Introduction 1
1.1 Fungi in human health 1
1.2 Virulence factors of Candida albicans 2
1.3 Specific intestinal epithelial cells 3
1.4 Mucus in the gastrointestinal tract 5
1.5 Candida infection animal model 5
1.6 Host immune responses during Candida albicans colonization and
infection 7
1.7 Purpose of the research 8
Chapter 2 Materials and methods 9
2.1 Fungal growth conditions 9
2.2 Cell culture 9
2.3 Invasion assay 10
2.4 Animal 10
2.5 Candida colonization and systemic candidiasis murine model 11
2.6 Immunofluorescence assay, IFA (Immunocytochemistry, ICC
and Immunohistochemistry, IHC) 11
2.7 Microscopy and image analysis 12
2.8 Isolation of mesenteric lymph node and lamina propria leukocytes 12
2.9 Cell staining and flow cytometry 13
2.10 Quantification and statistical analysis 14
Chapter 3 Results 15
3.1 Als3-mediated cell invasion in human and mouse E/N-cadherin expressing
cells 15
3.2 The Mice reared in conventional vivarium increased the amount of villous
M cell specifically in the ileum 16
3.3 Als3 is dispensable for C. albicans gut colonization in wild-type mice 17
3.4 Als3 prevented C. albicans from liver translocation in an IL-1β
deficiency-dependent manner 18
3.5 Als3 expression contributed to neutrophil recruitment in the small
intestinal lamina propria 19
3.6 Als3 is dispensable for the protective effect of C. albicans intestinal
colonization in systemic C. albicans infection 20
Chapter 4 Discussion 21
References 29
Figures 44
Tables 64








List of Figures


Figure 1. Als3 is not required for C. albicans to adhere to human and mouse
E/N-cadherin expressing cells 44
Figure 2. Als3 mediates C. albicans invasion into human and mouse cells
expressing E-cadherin or N-cadherin 45
Figure 3. als3 mutant strains reduced the invasion ability on human and mouse
E-cadherin expressing cells 46
Figure 4. als3 mutant strains reduced the invasion ability on human and mouse
N-cadherin expressing cells 47
Figure 5. NKM16-2-4+ villous M cell amount in ileum increases after
keeping in conventional vivarium 48
Figure 6. NKM16-2-4+ villous M cells located at the apical pole of the villus in
ileum 49
Figure 7. Broad-spectrum antibiotic treatment enhanced the
C. albicans colonization in wild-type mice 50
Figure 8. Als3 did not affect C. albicans gut colonization nor systemic infection
in wild-type mice 51
Figure 9. Broad-spectrum antibiotic treatment also enhanced the
C. albicans colonization in IL-1 KO mice 52
Figure 10. Als3 prevented C. albicans from liver translocation in IL-1 KO mice
53
Figure 11. C. albicans targeted to the villous M cell and goblet cell in IL-1 KO
mice 54
Figure 12. Als3 expression in C. albicans may induce CD11b+ mononuclear
phagocyte response in IL-1 KO mice 55

Figure 13. Gating strategy of CD11b+ mononuclear phagocytes and CD11b+
Ly6G+ neutrophils isolated from the murine lamina propria of the small intestine
or mesenteric lymph nodes 57
Figure 14. Als3 expression contributed to neutrophil recruitment in the small
intestine 59
Figure 15. The recruited neutrophils located in the lamina propria of the small
intestinal villus under wild-type C. albicans colonization 60
Figure 16. Als3 did not affect C. albicans gut colonization nor systemic infection
in wild-type mice 61
Figure 17. Illustration of Als3-mouse epithelial cell interaction 62
Figure 18. Schematic of Als3 characteristic in C. albicans murine colonization
model 63
















List of Tables


Table 1. Cell lines and Fungal strains 64
Table 2. Immunofluorescence staining 65

References

Albac, S., Schmitz, A., Lopez‐Alayon, C., d'Enfert, C., Sautour, M., Ducreux, A., Labruère‐Chazal, C., Laue, M., Holland, G., and Bonnin, A. (2016). Candida albicans is able to use M cells as a portal of entry across the intestinal barrier in vitro. Cellular microbiology 18, 195-210.
Altmeier, S., Toska, A., Sparber, F., Teijeira, A., Halin, C., and LeibundGut-Landmann, S. (2016). IL-1 coordinates the neutrophil response to C. albicans in the oral mucosa. PLoS pathogens 12, e1005882.
Arike, L., Holmén-Larsson, J., and Hansson, G.C. (2017). Intestinal Muc2 mucin O-glycosylation is affected by microbiota and regulated by differential expression of glycosyltranferases. Glycobiology 27, 318-328.
Aykut, B., Pushalkar, S., Chen, R., Li, Q., Abengozar, R., Kim, J.I., Shadaloey, S.A., Wu, D., Preiss, P., and Verma, N. (2019). The fungal mycobiome promotes pancreatic oncogenesis via activation of MBL. Nature 574, 264-267.
Böhm, L., Torsin, S., Tint, S.H., Eckstein, M.T., Ludwig, T., and Pérez, J.C. (2017). The yeast form of the fungus Candida albicans promotes persistence in the gut of gnotobiotic mice. PLoS pathogens 13, e1006699.
Bacher, P., Hohnstein, T., Beerbaum, E., Rocker, M., Blango, M.G., Kaufmann, S., Rohmel, J., Eschenhagen, P., Grehn, C., Seidel, K., et al. (2019). Human Anti-fungal Th17 Immunity and Pathology Rely on Cross-Reactivity against Candida albicans. Cell 176, 1340-1355 e1315.
Banerjee, A., McKinley, E.T., von Moltke, J., Coffey, R.J., and Lau, K.S. (2018). Interpreting heterogeneity in intestinal tuft cell structure and function. J Clin Invest 128, 1711-1719.
Benson, D.L., and Tanaka, H. (1998). N-cadherin redistribution during synaptogenesis in hippocampal neurons. Journal of Neuroscience 18, 6892-6904.
Berg, R.D. (1980). Inhibition of Escherichia coli translocation from the gastrointestinal tract by normal cecal flora in gnotobiotic or antibiotic-decontaminated mice. Infection and Immunity 29, 1073-1081.
Bergstrom, K.S., and Xia, L. (2013). Mucin-type O-glycans and their roles in intestinal homeostasis. Glycobiology 23, 1026-1037.
Birchenough, G.M., Nyström, E.E., Johansson, M.E., and Hansson, G.C. (2016). A sentinel goblet cell guards the colonic crypt by triggering Nlrp6-dependent Muc2 secretion. Science 352, 1535-1542.
Biton, M., Haber, A.L., Rogel, N., Burgin, G., Beyaz, S., Schnell, A., Ashenberg, O., Su, C.W., Smillie, C., Shekhar, K., et al. (2018). T Helper Cell Cytokines Modulate Intestinal Stem Cell Renewal and Differentiation. Cell 175, 1307-1320 e1322.
Bongomin, F., Gago, S., Oladele, R.O., and Denning, D.W. (2017). Global and multi-national prevalence of fungal diseases—estimate precision. Journal of fungi 3, 57.
Brown, J.H., and Sibly, R.M. (2006). Life-history evolution under a production constraint. Proceedings of the National Academy of Sciences 103, 17595-17599.
Cerovic, V., Bain, C.C., Mowat, A.M., and Milling, S.W. (2014). Intestinal macrophages and dendritic cells: what's the difference? Trends Immunol 35, 270-277.
Cerovic, V., Houston, S., Scott, C., Aumeunier, A., Yrlid, U., Mowat, A., and Milling, S. (2013). Intestinal CD103− dendritic cells migrate in lymph and prime effector T cells. Mucosal immunology 6, 104-113.
Cleary, I.A., Reinhard, S.M., Miller, C.L., Murdoch, C., Thornhill, M.H., Lazzell, A.L., Monteagudo, C., Thomas, D.P., and Saville, S.P. (2011). Candida albicans adhesin Als3p is dispensable for virulence in the mouse model of disseminated candidiasis. Microbiology 157, 1806.
Cohan, V.L., Scott, A.L., Dinarello, C.A., and Prendergast, R.A. (1991). Interleukin-1 is a mucus secretagogue. Cellular immunology 136, 425-434.
Coleman, D.A., Oh, S.H., Zhao, X., Zhao, H., Hutchins, J.T., Vernachio, J.H., Patti, J.M., and Hoyer, L.L. (2009). Monoclonal antibodies specific for Candida albicans Als3 that immunolabel fungal cells in vitro and in vivo and block adhesion to host surfaces. J Microbiol Methods 78, 71-78.
da Silva Dantas, A., Lee, K.K., Raziunaite, I., Schaefer, K., Wagener, J., Yadav, B., and Gow, N.A. (2016). Cell biology of Candida albicans–host interactions. Current opinion in microbiology 34, 111-118.
Dabbagh, K., Takeyama, K., Lee, H.-M., Ueki, I.F., Lausier, J.A., and Nadel, J.A. (1999). IL-4 induces mucin gene expression and goblet cell metaplasia in vitro and in vivo. The Journal of Immunology 162, 6233-6237.
Denning, D.W., Pleuvry, A., and Cole, D.C. (2013). Global burden of allergic bronchopulmonary aspergillosis with asthma and its complication chronic pulmonary aspergillosis in adults. Medical mycology 51, 361-370.
Diamond, R.D., and Krzesicki, R. (1978). Mechanisms of attachment of neutrophils to Candida albicans pseudohyphae in the absence of serum, and of subsequent damage to pseudohyphae by microbicidal processes of neutrophils in vitro. The Journal of Clinical Investigation 61, 360-369.
Dinarello, C.A., Simon, A., and Van Der Meer, J.W. (2012). Treating inflammation by blocking interleukin-1 in a broad spectrum of diseases. Nature reviews Drug discovery 11, 633-652.
Dobson, G.P., Letson, H.L., Biros, E., and Morris, J. (2019). Specific pathogen-free (SPF) animal status as a variable in biomedical research: Have we come full circle? EBioMedicine 41, 42-43.
Downward, J.R.E., Falkowski, N.R., Mason, K.L., Muraglia, R., and Huffnagle, G.B. (2013). Modulation of post-antibiotic bacterial community reassembly and host response by Candida albicans. Scientific reports 3, 2191.
Ermund, A., Schütte, A., Johansson, M.E., Gustafsson, J.K., and Hansson, G.C. (2013). Studies of mucus in mouse stomach, small intestine, and colon. I. Gastrointestinal mucus layers have different properties depending on location as well as over the Peyer's patches. American Journal of Physiology-Gastrointestinal and Liver Physiology 305, G341-G347.
Esterhazy, D., Loschko, J., London, M., Jove, V., Oliveira, T.Y., and Mucida, D. (2016). Classical dendritic cells are required for dietary antigen-mediated induction of peripheral T(reg) cells and tolerance. Nat Immunol 17, 545-555.
Fan, Y., He, H., Dong, Y., and Pan, H. (2013). Hyphae-specific genes HGC1, ALS3, HWP1, and ECE1 and relevant signaling pathways in Candida albicans. Mycopathologia 176, 329-335.
Fischinger, S., Boudreau, C.M., Butler, A.L., Streeck, H., and Alter, G. (2019). Sex differences in vaccine-induced humoral immunity. Paper presented at: Seminars in Immunopathology (Springer).
Flanagan, K.L., Fink, A.L., Plebanski, M., and Klein, S.L. (2017). Sex and gender differences in the outcomes of vaccination over the life course. Annual Review of Cell and Developmental Biology 33, 577-599.
Flannigan, K.L., Ngo, V.L., Geem, D., Harusato, A., Hirota, S.A., Parkos, C.A., Lukacs, N.W., Nusrat, A., Gaboriau-Routhiau, V., and Cerf-Bensussan, N. (2017). IL-17A-mediated neutrophil recruitment limits expansion of segmented filamentous bacteria. Mucosal immunology 10, 673-684.
Fu, Y., Ibrahim, A.S., Fonzi, W., Zhou, X., Ramos, C.F., and Ghannoum, M.A. (1997). Cloning and characterization of a gene (LIP1) which encodes a lipase from the pathogenic yeast Candida albicans. Microbiology 143, 331-340.
Fu, Y., Phan, Q.T., Luo, G., Solis, N.V., Liu, Y., Cormack, B.P., Edwards, J.E., Ibrahim, A.S., and Filler, S.G. (2013). Investigation of the function of Candida albicans Als3 by heterologous expression in Candida glabrata. Infection and immunity 81, 2528-2535.
Gabaldón, T., and Fairhead, C. (2019). Genomes shed light on the secret life of Candida glabrata: not so asexual, not so commensal. Current genetics 65, 93-98.
Ge, X., Ding, C., Zhao, W., Xu, L., Tian, H., Gong, J., Zhu, M., Li, J., and Li, N. (2017). Antibiotics-induced depletion of mice microbiota induces changes in host serotonin biosynthesis and intestinal motility. Journal of translational medicine 15, 1-9.
Gribble, F.M., and Reimann, F. (2019). Function and mechanisms of enteroendocrine cells and gut hormones in metabolism. Nature Reviews Endocrinology 15, 226-237.
Gu, Z.-Q., Tseng, K.-Y., and Tsai, Y.-H. (2020). Candida gut commensalism and inflammatory disease. Medicine in Microecology, 100008.
Gustafsson, J.K., Ermund, A., Johansson, M.E., Schütte, A., Hansson, G.C., and Sjövall, H. (2012). An ex vivo method for studying mucus formation, properties, and thickness in human colonic biopsies and mouse small and large intestinal explants. American Journal of Physiology-Gastrointestinal and Liver Physiology 302, G430-G438.
Hise, A.G., Tomalka, J., Ganesan, S., Patel, K., Hall, B.A., Brown, G.D., and Fitzgerald, K.A. (2009). An essential role for the NLRP3 inflammasome in host defense against the human fungal pathogen Candida albicans. Cell host & microbe 5, 487-497.
Holmén Larsson, J.M., Thomsson, K.A., Rodríguez-Piñeiro, A.M., Karlsson, H., and Hansson, G.C. (2013). Studies of mucus in mouse stomach, small intestine, and colon. III. Gastrointestinal Muc5ac and Muc2 mucin O-glycan patterns reveal a regiospecific distribution. American Journal of Physiology-Gastrointestinal and Liver Physiology 305, G357-G363.
Hoyer, L.L., Payne, T.L., Bell, M., Myers, A.M., and Scherer, S. (1998). Candida albicans ALS3 and insights into the nature of the ALS gene family. Current genetics 33, 451-459.
Hsueh, P.-R., Teng, L.-J., Yang, P.-C., Ho, S.-W., and Luh, K.-T. (2002). Emergence of nosocomial candidemia at a teaching hospital in Taiwan from 1981 to 2000: increased susceptibility of Candida species to fluconazole. Microbial Drug Resistance 8, 311-319.
Hube, B. (2004). From commensal to pathogen: stage-and tissue-specific gene expression of Candida albicans. Current opinion in microbiology 7, 336-341.
Ibrahim, A.S., Mirbod, F., Filler, S.G., Banno, Y., Cole, G.T., Kitajima, Y., Edwards, J., Nozawa, Y., and Ghannoum, M.A. (1995). Evidence implicating phospholipase as a virulence factor of Candida albicans. Infection and immunity 63, 1993-1998.
Iliev, I.D., Funari, V.A., Taylor, K.D., Nguyen, Q., Reyes, C.N., Strom, S.P., Brown, J., Becker, C.A., Fleshner, P.R., and Dubinsky, M. (2012). Interactions between commensal fungi and the C-type lectin receptor Dectin-1 influence colitis. Science 336, 1314-1317.
Imam, N., Carpenter, C.C., Mayer, K.H., Fisher, A., Stein, M., and Danforth, S.B. (1990). Hierarchical pattern of mucosal Candida infections in HIV-seropositive women. The American journal of medicine 89, 142-146.
Ivanov, I.I., Atarashi, K., Manel, N., Brodie, E.L., Shima, T., Karaoz, U., Wei, D., Goldfarb, K.C., Santee, C.A., and Lynch, S.V. (2009). Induction of intestinal Th17 cells by segmented filamentous bacteria. Cell 139, 485-498.
Ivanov, I.I., de Llanos Frutos, R., Manel, N., Yoshinaga, K., Rifkin, D.B., Sartor, R.B., Finlay, B.B., and Littman, D.R. (2008). Specific microbiota direct the differentiation of IL-17-producing T-helper cells in the mucosa of the small intestine. Cell host & microbe 4, 337-349.
Iwai, Y., Usui, T., Hirano, S., Steward, R., Takeichi, M., and Uemura, T. (1997). Axon patterning requires D N-cadherin, a novel neuronal adhesion receptor, in the Drosophila embryonic CNS. Neuron 19, 77-89.
Jaeger, M., Pinelli, M., Borghi, M., Constantini, C., Dindo, M., van Emst, L., Puccetti, M., Pariano, M., Ricaño-Ponce, I., and Büll, C. (2019). A systems genomics approach identifies SIGLEC15 as a susceptibility factor in recurrent vulvovaginal candidiasis. Science translational medicine 11, eaar3558.
Jang, M.H., Kweon, M.-N., Iwatani, K., Yamamoto, M., Terahara, K., Sasakawa, C., Suzuki, T., Nochi, T., Yokota, Y., and Rennert, P.D. (2004). Intestinal villous M cells: an antigen entry site in the mucosal epithelium. Proceedings of the National Academy of Sciences 101, 6110-6115.
Johansson, M.E., Larsson, J.M.H., and Hansson, G.C. (2011). The two mucus layers of colon are organized by the MUC2 mucin, whereas the outer layer is a legislator of host–microbial interactions. Proceedings of the national academy of sciences 108, 4659-4665.
Kamai, Y., Kubota, M., Kamai, Y., Hosokawa, T., Fukuoka, T., and Filler, S.G. (2002). Contribution of Candida albicans ALS1 to the pathogenesis of experimental oropharyngeal candidiasis. Infection and immunity 70, 5256-5258.
Kapitan, M., Niemiec, M.J., Steimle, A., Frick, J.S., and Jacobsen, I.D. (2018). Fungi as part of the microbiota and interactions with intestinal bacteria. In Fungal Physiology and Immunopathogenesis (Springer), pp. 265-301.
Kastl Jr, A.J., Terry, N.A., Wu, G.D., and Albenberg, L.G. (2020). The structure and function of the human small intestinal microbiota: current understanding and future directions. Cellular and molecular gastroenterology and hepatology 9, 33-45.
Kavanaugh, N.L., Zhang, A.Q., Nobile, C.J., Johnson, A.D., and Ribbeck, K. (2014). Mucins suppress virulence traits of Candida albicans. MBio 5.
Kennedy, M.J., and Volz, P.A. (1985). Effect of various antibiotics on gastrointestinal colonization and dissemination by Candida albicans. Sabouraudia: Journal of Medical and Veterinary Mycology 23, 265-273.
Kim, Y.S., and Ho, S.B. (2010). Intestinal goblet cells and mucins in health and disease: recent insights and progress. Current gastroenterology reports 12, 319-330.
Kinoshita, M., Uchida, T., Sato, A., Nakashima, M., Nakashima, H., Shono, S., Habu, Y., Miyazaki, H., Hiroi, S., and Seki, S. (2010). Characterization of two F4/80-positive Kupffer cell subsets by their function and phenotype in mice. Journal of hepatology 53, 903-910.
Koh, A.Y., Köhler, J.R., Coggshall, K.T., Van Rooijen, N., and Pier, G.B. (2008). Mucosal damage and neutropenia are required for Candida albicans dissemination. PLoS Pathog 4, e35.
Koyama, M., Mukhopadhyay, P., Schuster, I.S., Henden, A.S., Hulsdunker, J., Varelias, A., Vetizou, M., Kuns, R.D., Robb, R.J., Zhang, P., et al. (2019). MHC Class II Antigen Presentation by the Intestinal Epithelium Initiates Graft-versus-Host Disease and Is Influenced by the Microbiota. Immunity 51, 885-898 e887.
Krüger, W., Vielreicher, S., Kapitan, M., Jacobsen, I.D., and Niemiec, M.J. (2019). Fungal-bacterial interactions in health and disease. Pathogens 8, 70.
Lachke, S.A., Srikantha, T., Tsai, L.K., Daniels, K., and Soll, D.R. (2000). Phenotypic switching in Candida glabrata involves phase-specific regulation of the Metallothionein gene MT-IIand the newly discovered hemolysin gene HLP. Infection and immunity 68, 884-895.
Lamkanfi, M., and Dixit, V.M. (2011). Modulation of inflammasome pathways by bacterial and viral pathogens. The Journal of Immunology 187, 597-602.
LeibundGut-Landmann, S., Groß, O., Robinson, M.J., Osorio, F., Slack, E.C., Tsoni, S.V., Schweighoffer, E., Tybulewicz, V., Brown, G.D., and Ruland, J. (2007). Syk-and CARD9-dependent coupling of innate immunity to the induction of T helper cells that produce interleukin 17. Nature immunology 8, 630-638.
Leidich, S.D., Ibrahim, A.S., Fu, Y., Koul, A., Jessup, C., Vitullo, J., Fonzi, W., Mirbod, F., Nakashima, S., and Nozawa, Y. (1998). Cloning and disruption of caPLB1, a phospholipase B gene involved in the pathogenicity of Candida albicans. Journal of Biological Chemistry 273, 26078-26086.
Leonardi, I., Li, X., Semon, A., Li, D., Doron, I., Putzel, G., Bar, A., Prieto, D., Rescigno, M., and McGovern, D.P. (2018). CX3CR1+ mononuclear phagocytes control immunity to intestinal fungi. Science 359, 232-236.
Li, X., Leonardi, I., Semon, A., Doron, I., Gao, I.H., Putzel, G.G., Kim, Y., Kabata, H., Artis, D., and Fiers, W.D. (2018). Response to fungal dysbiosis by gut-resident CX3CR1+ mononuclear phagocytes aggravates allergic airway disease. Cell host & microbe 24, 847-856. e844.
Lin, J., Oh, S.H., Jones, R., Garnett, J.A., Salgado, P.S., Rusnakova, S., Matthews, S.J., Hoyer, L.L., and Cota, E. (2014). The peptide-binding cavity is essential for Als3-mediated adhesion of Candida albicans to human cells. J Biol Chem 289, 18401-18412.
Liu, C.-Y., Liao, C.-H., Chen, Y.-C., and Chang, S.-C. (2010). Changing epidemiology of nosocomial bloodstream infections in 11 teaching hospitals in Taiwan between 1993 and 2006. Journal of Microbiology, Immunology and Infection 43, 416-429.
Liu, Y., and Filler, S.G. (2011). Candida albicans Als3, a multifunctional adhesin and invasin. Eukaryot Cell 10, 168-173.
Lo, H.-J., Köhler, J.R., DiDomenico, B., Loebenberg, D., Cacciapuoti, A., and Fink, G.R. (1997). Nonfilamentous C. albicans mutants are avirulent. Cell 90, 939-949.
Luissint, A.-C., Williams, H.C., Kim, W., Flemming, S., Azcutia, V., Hilgarth, R.S., O’Leary, M.N., Denning, T.L., Nusrat, A., and Parkos, C.A. (2019). Macrophage-dependent neutrophil recruitment is impaired under conditions of increased intestinal permeability in JAM-A-deficient mice. Mucosal immunology 12, 668-678.
Luo, G., Samaranayake, L.P., and Yau, J.Y. (2001). Candida species exhibit differential in vitro hemolytic activities. Journal of Clinical Microbiology 39, 2971-2974.
Lyon, J.P., da Costa, S.C., Totti, V.M.G., Munhoz, M.F.V., and de Resende, M.A. (2006). Predisposing conditions for Candida spp. carriage in the oral cavity of denture wearers and individuals with natural teeth. Canadian journal of microbiology 52, 462-467.
Mason, K.L., Downward, J.R.E., Mason, K.D., Falkowski, N.R., Eaton, K.A., Kao, J.Y., Young, V.B., and Huffnagle, G.B. (2012). Candida albicans and bacterial microbiota interactions in the cecum during recolonization following broad-spectrum antibiotic therapy. Infection and immunity 80, 3371-3380.
Meis, J.F., Ruhnke, M., De Pauw, B.E., Odds, F.C., Siegert, W., and Verweij, P.E. (1999). Candida dubliniensis candidemia in patients with chemotherapy-induced neutropenia and bone marrow transplantation. Emerging infectious diseases 5, 150.
Miron, N., and Cristea, V. (2012). Enterocytes: active cells in tolerance to food and microbial antigens in the gut. Clinical & Experimental Immunology 167, 405-412.
Monroy-Pérez, E., Paniagua-Contreras, G.L., Rodríguez-Purata, P., Vaca-Paniagua, F., Vázquez-Villaseñor, M., Díaz-Velásquez, C., Uribe-García, A., and Vaca, S. (2016). High virulence and antifungal resistance in clinical strains of Candida albicans. Canadian Journal of Infectious Diseases and Medical Microbiology 2016.
Moyes, D.L., Wilson, D., Richardson, J.P., Mogavero, S., Tang, S.X., Wernecke, J., Höfs, S., Gratacap, R.L., Robbins, J., and Runglall, M. (2016). Candidalysin is a fungal peptide toxin critical for mucosal infection. Nature 532, 64-68.
Naglik, J., Albrecht, A., Bader, O., and Hube, B. (2004). Candida albicans proteinases and host/pathogen interactions. Cellular microbiology 6, 915-926.
Naglik, J.R., Challacombe, S.J., and Hube, B. (2003). Candida albicans secreted aspartyl proteinases in virulence and pathogenesis. Microbiology and molecular biology reviews 67, 400-428.
Nikitas, G., Deschamps, C., Disson, O., Niault, T., Cossart, P., and Lecuit, M. (2011). Transcytosis of Listeria monocytogenes across the intestinal barrier upon specific targeting of goblet cell accessible E-cadherin. J Exp Med 208, 2263-2277.
Nikou, S.-A., Kichik, N., Brown, R., Ponde, N.O., Ho, J., Naglik, J.R., and Richardson, J.P. (2019). Candida albicans interactions with mucosal surfaces during health and disease. Pathogens 8, 53.
Noble, S.M., Gianetti, B.A., and Witchley, J.N. (2017). Candida albicans cell-type switching and functional plasticity in the mammalian host. Nature Reviews Microbiology 15, 96.
Nochi, T., Yuki, Y., Matsumura, A., Mejima, M., Terahara, K., Kim, D.Y., Fukuyama, S., Iwatsuki-Horimoto, K., Kawaoka, Y., Kohda, T., et al. (2007). A novel M cell-specific carbohydrate-targeted mucosal vaccine effectively induces antigen-specific immune responses. J Exp Med 204, 2789-2796.
Oh, S.-H., Cheng, G., Nuessen, J.A., Jajko, R., Yeater, K.M., Zhao, X., Pujol, C., Soll, D.R., and Hoyer, L.L. (2005). Functional specificity of Candida albicans Als3p proteins and clade specificity of ALS3 alleles discriminated by the number of copies of the tandem repeat sequence in the central domain. Microbiology 151, 673-681.
Ohne, Y., Silver, J.S., Thompson-Snipes, L., Collet, M.A., Blanck, J.P., Cantarel, B.L., Copenhaver, A.M., Humbles, A.A., and Liu, Y.J. (2016). IL-1 is a critical regulator of group 2 innate lymphoid cell function and plasticity. Nat Immunol 17, 646-655.
Ott, S.J., Kühbacher, T., Musfeldt, M., Rosenstiel, P., Hellmig, S., Rehman, A., Drews, O., Weichert, W., Timmis, K.N., and Schreiber, S. (2008). Fungi and inflammatory bowel diseases: alterations of composition and diversity. Scandinavian journal of gastroenterology 43, 831-841.
Phan, Q.T., Myers, C.L., Fu, Y., Sheppard, D.C., Yeaman, M.R., Welch, W.H., Ibrahim, A.S., Edwards, J.E., Jr., and Filler, S.G. (2007). Als3 is a Candida albicans invasin that binds to cadherins and induces endocytosis by host cells. PLoS Biol 5, e64.
Pietrella, D., Pandey, N., Gabrielli, E., Pericolini, E., Perito, S., Kasper, L., Bistoni, F., Cassone, A., Hube, B., and Vecchiarelli, A. (2013). Secreted aspartic proteases of C andida albicans activate the NLRP 3 inflammasome. European journal of immunology 43, 679-692.
Plaine, A., Walker, L., Da Costa, G., Mora-Montes, H.M., McKinnon, A., Gow, N.A., Gaillardin, C., Munro, C.A., and Richard, M.L. (2008). Functional analysis of Candida albicans GPI-anchored proteins: roles in cell wall integrity and caspofungin sensitivity. Fungal Genetics and Biology 45, 1404-1414.
Porter, E., Bevins, C.L., Ghosh, D., and Ganz, T. (2002). The multifaceted Paneth cell. Cellular and molecular life sciences CMLS 59, 156-170.
Price, M.F., Wilkinson, I.D., and Gentry, L.O. (1982). Plate method for detection of phospholipase activity in Candida albicans. Sabouraudia: Journal of Medical and Veterinary Mycology 20, 7-14.
Raetz, M., Hwang, S.-h., Wilhelm, C.L., Kirkland, D., Benson, A., Sturge, C.R., Mirpuri, J., Vaishnava, S., Hou, B., and DeFranco, A.L. (2013). Parasite-induced T H 1 cells and intestinal dysbiosis cooperate in IFN-γ-dependent elimination of Paneth cells. Nature immunology 14, 136.
Rajasingham, R., Smith, R.M., Park, B.J., Jarvis, J.N., Govender, N.P., Chiller, T.M., Denning, D.W., Loyse, A., and Boulware, D.R. (2017). Global burden of disease of HIV-associated cryptococcal meningitis: an updated analysis. The Lancet infectious diseases 17, 873-881.
Revankar, S.G., and Sutton, D.A. (2010). Melanized fungi in human disease. Clinical Microbiology Reviews 23, 884-928.
Rizzetto, L., Ifrim, D.C., Moretti, S., Tocci, N., Cheng, S.-C., Quintin, J., Renga, G., Oikonomou, V., De Filippo, C., and Weil, T. (2016). Fungal chitin induces trained immunity in human monocytes during cross-talk of the host with Saccharomyces cerevisiae. Journal of Biological Chemistry 291, 7961-7972.
Rodríguez-Piñeiro, A.M., Bergström, J.H., Ermund, A., Gustafsson, J.K., Schütte, A., Johansson, M.E., and Hansson, G.C. (2013). Studies of mucus in mouse stomach, small intestine, and colon. II. Gastrointestinal mucus proteome reveals Muc2 and Muc5ac accompanied by a set of core proteins. American Journal of Physiology-Gastrointestinal and Liver Physiology 305, G348-G356.
Rosshart, S.P., Herz, J., Vassallo, B.G., Hunter, A., Wall, M.K., Badger, J.H., McCulloch, J.A., Anastasakis, D.G., Sarshad, A.A., Leonardi, I., et al. (2019). Laboratory mice born to wild mice have natural microbiota and model human immune responses. Science 365.
Sacristan, B., Blanco, M., Galan-Ladero, M., Blanco, J., Perez-Giraldo, C., and Gomez-Garcia, A. (2011). Aspartyl proteinase, phospholipase, hemolytic activities and biofilm production of Candida albicans isolated from bronchial aspirates of ICU patients. Medical mycology 49, 94-97.
Sangeorzan, J.A., Bradley, S.F., He, X., Zarins, L.T., Ridenour, G.L., Tiballi, R.N., and Kauffman, C.A. (1994). Epidemiology of oral candidiasis in HIV-infected patients: colonization, infection, treatment, and emergence of fluconazole resistance. The American journal of medicine 97, 339-346.
Sartor, R.B. (2008). Microbial influences in inflammatory bowel diseases. Gastroenterology 134, 577-594.
Schaller, M., Borelli, C., Korting, H.C., and Hube, B. (2005). Hydrolytic enzymes as virulence factors of Candida albicans. Mycoses 48, 365-377.
Schulze, J., and Sonnenborn, U. (2009). Yeasts in the gut: from commensals to infectious agents. Deutsches Ärzteblatt International 106, 837.
Seelig, M.S. (1966). Mechanisms by which antibiotics increase the incidence and severity of candidiasis and alter the immunological defenses. Bacteriological reviews 30, 442.
Shao, T.Y., Ang, W.X.G., Jiang, T.T., Huang, F.S., Andersen, H., Kinder, J.M., Pham, G., Burg, A.R., Ruff, B., Gonzalez, T., et al. (2019). Commensal Candida albicans Positively Calibrates Systemic Th17 Immunological Responses. Cell Host Microbe 25, 404-417 e406.
Smolenski, G., Sullivan, P., Cutfield, S., and Cutfield, J. (1997). Analysis of secreted aspartic proteinases from Candida albicans: purification and characterization of individual Sap1, Sap2 and Sap3 isoenzymes. Microbiology 143, 349-356.
Sun, D., Sun, P., Li, H., Zhang, M., Liu, G., Strickland, A.B., Chen, Y., Fu, Y., Xu, J., and Yosri, M. (2019). Fungal dissemination is limited by liver macrophage filtration of the blood. Nature communications 10, 1-14.
Sun, J.N., Solis, N.V., Phan, Q.T., Bajwa, J.S., Kashleva, H., Thompson, A., Liu, Y., Dongari-Bagtzoglou, A., Edgerton, M., and Filler, S.G. (2010). Host cell invasion and virulence mediated by Candida albicans Ssa1. PLoS Pathog 6, e1001181.
Swamydas, M., Gao, J.-L., Break, T.J., Johnson, M.D., Jaeger, M., Rodriguez, C.A., Lim, J.K., Green, N.M., Collar, A.L., and Fischer, B.G. (2016). CXCR1-mediated neutrophil degranulation and fungal killing promote Candida clearance and host survival. Science translational medicine 8, 322ra310-322ra310.
Swidergall, M., Solis, N.V., Millet, N., Huang, M.Y., Lin, J., Phan, Q.T., Lazarus, M.D., Wang, Z., Mitchell, A.P., and Filler, S.G. (2020). Activation of oral epithelial EphA2-EFGR signaling by Candida albicans virulence factors. bioRxiv, 491076.
Tan, Z.-J., Peng, Y., Song, H.-L., Zheng, J.-J., and Yu, X. (2010). N-cadherin-dependent neuron–neuron interaction is required for the maintenance of activity-induced dendrite growth. Proceedings of the National Academy of Sciences 107, 9873-9878.
Tati, S., Davidow, P., McCall, A., Hwang-Wong, E., Rojas, I.G., Cormack, B., and Edgerton, M. (2016). Candida glabrata binding to Candida albicans hyphae enables its development in oropharyngeal candidiasis. PLoS pathogens 12, e1005522.
Terahara, K., Yoshida, M., Igarashi, O., Nochi, T., Pontes, G.S., Hase, K., Ohno, H., Kurokawa, S., Mejima, M., and Takayama, N. (2008). Comprehensive gene expression profiling of Peyer’s patch M cells, villous M-like cells, and intestinal epithelial cells. The Journal of Immunology 180, 7840-7846.
Tsai, Y.H., Disson, O., Bierne, H., and Lecuit, M. (2013). Murinization of internalin extends its receptor repertoire, altering Listeria monocytogenes cell tropism and host responses. PLoS Pathog 9, e1003381.
Tso, G.H.W., Reales-Calderon, J.A., Tan, A.S.M., Sem, X., Le, G.T.T., Tan, T.G., Lai, G.C., Srinivasan, K., Yurieva, M., and Liao, W. (2018). Experimental evolution of a fungal pathogen into a gut symbiont. Science 362, 589-595.
van der Flier, L.G., and Clevers, H. (2009). Stem cells, self-renewal, and differentiation in the intestinal epithelium. Annu Rev Physiol 71, 241-260.
Vautier, S., Drummond, R.A., Chen, K., Murray, G.I., Kadosh, D., Brown, A.J., Gow, N.A., MacCallum, D.M., Kolls, J.K., and Brown, G.D. (2015). C andida albicans colonization and dissemination from the murine gastrointestinal tract: the influence of morphology and T h17 immunity. Cellular microbiology 17, 445-450.
Verma, A.H., Richardson, J.P., Zhou, C., Coleman, B.M., Moyes, D.L., Ho, J., Huppler, A.R., Ramani, K., McGeachy, M.J., and Mufazalov, I.A. (2017). Oral epithelial cells orchestrate innate type 17 responses to Candida albicans through the virulence factor candidalysin. Science immunology 2.
von Moltke, J., Ji, M., Liang, H.-E., and Locksley, R.M. (2016). Tuft-cell-derived IL-25 regulates an intestinal ILC2–epithelial response circuit. Nature 529, 221-225.
Vonk, A.G., Netea, M.G., Van Krieken, J.H., Iwakura, Y., Van Der Meer, J.W., and Kullberg, B.J. (2006). Endogenous interleukin (IL)–1α and IL-1β are crucial for host defense against disseminated candidiasis. The Journal of infectious diseases 193, 1419-1426.
Waddell, A., Vallance, J.E., Hummel, A., Alenghat, T., and Rosen, M.J. (2019). IL-33 induces murine intestinal goblet cell differentiation indirectly via innate lymphoid cell IL-13 secretion. The Journal of Immunology 202, 598-607.
Witchley, J.N., Penumetcha, P., Abon, N.V., Woolford, C.A., Mitchell, A.P., and Noble, S.M. (2019). Candida albicans Morphogenesis Programs Control the Balance between Gut Commensalism and Invasive Infection. Cell Host Microbe 25, 432-443 e436.
Zhai, B., Ola, M., Rolling, T., Tosini, N.L., Joshowitz, S., Littmann, E.R., Amoretti, L.A., Fontana, E., Wright, R.J., Miranda, E., et al. (2020). High-resolution mycobiota analysis reveals dynamic intestinal translocation preceding invasive candidiasis. Nat Med 26, 59-64.
Zhou, R., Yazdi, A.S., Menu, P., and Tschopp, J. (2011). A role for mitochondria in NLRP3 inflammasome activation. Nature 469, 221-225.
Zunder, T., Huber, R., Sander, A., Daschner, F., and Frank, U. (2002). The pathogenetic significance of intestinal Candida colonization–a systematic review from an interdisciplinary and environmental medical point of view. International journal of hygiene and environmental health 205, 257-268.