The Macrophage-Inducible C-Type Lectin, Mincle, Is an Essential Component of the Innate Immune Response to <i>Candida albicans</i>

Wells, Christine A.; Salvage-Jones, Judith; Li, Xin; Hitchens, Kelly; Butcher, Suzanne; Murray, Rachael Z.; Beckhouse, Anthony G; Lo, Yu-Lan-Sandra; Manzanero, Silvia; Cobbold, Christian; Schroder, Kate; Ma, Bin-Guang; Orr, Sally L.; Stewart, Lauren; Lebus, Daniel; Sobieszczuk, Peter; Hume, David; Stow, Jennifer L.; Blanchard, Helen; Ashman, R. B.

doi:10.4049/jimmunol.180.11.7404

Cited by 395 publications

(379 citation statements)

References 42 publications

(35 reference statements)

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“…It is shown to play a role in murine macrophage responses to yeast-form C. albicans. 114 Similar to Dectin-2, Mincle recognizes C. albicans by selectively binding a-mannose with the association of FcgR. 114 In human monocyte and neutrophil, Mincle expression is up-regulated upon C. albicans stimulus and further immune responses are thereby regulated.…”

Section: Prrs Of Neutrophils and Monocytes/macrophagesmentioning

confidence: 99%

“…114 Similar to Dectin-2, Mincle recognizes C. albicans by selectively binding a-mannose with the association of FcgR. 114 In human monocyte and neutrophil, Mincle expression is up-regulated upon C. albicans stimulus and further immune responses are thereby regulated. 115 CR3 and Dectin-1 are revealed to recognize C. albicans b-glucans.…”

Section: Prrs Of Neutrophils and Monocytes/macrophagesmentioning

confidence: 99%

“…49,51,142,143 Similarly, fungal recognition by Mincle induces the production of cytokines, including MIP-2, KC, IL-10 and TNF-a. 107,114 PRRs of dendritic cells (DCs)…”

Section: Prrs Of Neutrophils and Monocytes/macrophagesmentioning

confidence: 99%

See 2 more Smart Citations

The role of pattern recognition receptors in the innate recognition ofCandida albicans

Zheng

Wang

et al. 2015

Virulence

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Section: Prrs Of Neutrophils and Monocytes/macrophagesmentioning

confidence: 99%

Section: Prrs Of Neutrophils and Monocytes/macrophagesmentioning

confidence: 99%

See 1 more Smart Citation

The role of pattern recognition receptors in the innate recognition ofCandida albicans

Zheng

Wang

et al. 2015

Virulence

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“…Macrophage-inducible C-type lectin (Mincle, Clec4e or Clecsf9) is a pathogen sensor that recognizes pathogenic fungi and Mycobacterium tuberculosis [13][14][15][16] , and as the name implies, it is induced in macrophages by lipopolysaccharide through Toll-like receptor 4 (TLR4; ref. 17).…”

mentioning

confidence: 99%

Macrophage-inducible C-type lectin underlies obesity-induced adipose tissue fibrosis

et al. 2014

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“…Five C-type lectins also demonstrated increased expression during infection, including Clec7a (Dectin-1) and Clec4e, pattern-recognition receptors critical to combating other fungal pathogens (13)(14)(15). Indeed, a splice variant of Clec7a was identified as a major determinant of Coccidioides immitis infection outcome in mice (15).…”

Section: Resultsmentioning

confidence: 99%

Genetic control of immune cell types in fungal disease

Mayfield

Fontana

Rine

2010

Proc. Natl. Acad. Sci. U.S.A.

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Millions of people harbor latent infections of the fungus Histoplasma capsulatum. Such persistent infections represent a stalemate between mechanisms of virulence and the immune response. The differing responses of inbred mouse strains to the same pathogen reflect variation in the genes that control the outcome of infection. Here we show that a 250-fold difference in H. capsulatum susceptibility between inbred mouse strains is attributable to the genotype at the MHC H2 locus. Gene expression analysis of strains varying only at the H2 locus identified genotype-specific and genotype-independent expression signatures, including infection-induced genes such as the fungal pattern recognition receptor Clec7a. Surprisingly, B-cell-specific gene expression was negatively correlated with fungal burden, whereas neutrophil-specific genes were correlated with superior disease outcome. Indeed, disease outcome improved when B cells were eliminated and neutrophils were more active, a previously unknown aspect of the host response. These data refine the understanding of genetic influences on histoplasmosis, reveal how shifts in the composition of immune cell populations compel different disease outcomes, and uncover how innate immunity modulation alters histoplasmosis.G enetic differences among individuals can have profound effects on infectious disease susceptibility and severity; for example, severe infections with the dimorphic fungal pathogen Coccidioides immitis are more frequent in males and people of African or Asian descent (1). This relationship inspires the hope that uncovering the pivotal genes affecting disease outcome might lead to new therapeutic strategies for controlling disease. For histoplasmosis, a fungal pneumonia affecting millions of people worldwide (2), infection outcomes vary greatly among mouse strains with only minor differences in cytokine profiles (3, 4). Although molecular ablation has connected an orderly and well-defined cytokine response to histoplasmosis outcome (5-7), previous mouse strain studies have highlighted the unexplained aspects of a successful immune response. The experiments reported herein identify a major influence of the H2 locus on experimental infections of mice with the fungal pathogen Histoplasma capsulatum, uncover gene expression signatures of neutrophils and B cells in resistant strains of mice, show that B cells impair the antifungal response, and implicate the innate immune system as an early control point. ResultsGenetic Control of Disease Outcome After H. capsulatum Infection.We previously mapped quantitative trait loci controlling the phenotype of fungal burden using recombinant inbred mice (3). These data identify two regions on chromosome 17 linked to 250-fold lower fungal burden in the spleens of resistant A/J mice compared with sensitive C57BL/6 (B6) mice. One of those regions is tightly linked to the MHC H2, a highly variable multigene complex encoding the proteins responsible for antigen presentation. To test the contribution of the H2 locus to the immune respon...

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The Macrophage-Inducible C-Type Lectin, Mincle, Is an Essential Component of the Innate Immune Response to Candida albicans

Cited by 395 publications

References 42 publications

The role of pattern recognition receptors in the innate recognition ofCandida albicans

The role of pattern recognition receptors in the innate recognition ofCandida albicans

Macrophage-inducible C-type lectin underlies obesity-induced adipose tissue fibrosis

Genetic control of immune cell types in fungal disease

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