CD8<sup>+</sup>T Cells but Not Polymorphonuclear Leukocytes Are Required To Limit Chronic Oral Carriage of<i>Candida albicans</i>in Transgenic Mice Expressing Human Immunodeficiency Virus Type 1

Marquis, Miriam; Lewandowski, Daniel; Dugas, Véronique; Aumont, Francine; Sénéchal, Serge; Jolicoeur, Paul; Hanna, Zaher; Repentigny, Louis de

doi:10.1128/iai.74.4.2382-2391.2006

Cited by 32 publications

(30 citation statements)

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“…This clearly indicates that crosspresentation of fungi results in the activation of CD8 + T cells in vivo. CD4 + T cells are the most important anti-fungal effector cells of the adaptive immune system, but in the absence of CD4 + T cells, CD8 + T cell-mediated effector functions can play an important role [55][56][57]. Obviously, the CD8 + T cell-mediated anti-fungal response is particularly important for HIV patients.…”

Section: Discussionmentioning

confidence: 99%

CD8^– dendritic cells preferentially cross‐present Saccharomyces cerevisiae antigens

et al. 2008

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Mouse splenic dendritic cell (DC) subsets possess distinct antigen-presentation abilities. CD8 + DC are specialized in cross-presentation of antigens to CD8 + T cells, whereas CD8 -DC are more efficient in antigen presentation to CD4 + T cells. In this study, we examined the capacity of CD8 + and CD8 -DC subsets to present fungal antigens in MHC class I and II molecules to CD8 + and CD4 + T cells, respectively. We used ovalbuminexpressing Saccharomyces cerevisiae (yeast-OVA) as a fungal model system. Both CD8 + and CD8 -DC subsets phagocytosed yeast in equal amounts and uptake was mediated via dectin-1. In addition, both DC subsets induced similar OVA-specific CD4 + T cell proliferation after incubation with yeast-OVA. However, the induction of OVA-specific CD8 + T cell activation was largely restricted to the CD8 -DC subset. Furthermore, only CD8 -DC produced cytokines such as IL-10 and TNF-a and increased IL-23p19 and IL-23p40 mRNA levels in response to yeast. Our results strongly suggest that DC subsets have different functions in the elicitation of adaptive immune responses in vivo. IntroductionFungal infections with pathogenic yeasts such as Candida albicans, Aspergillus fumigatus, Histoplasma capsulatum and Cryptococcus neoformans are a major problem in immunocompromised persons. These opportunistic pathogens usually do not pose problems in healthy individuals, but frequently become invasive in patients suffering from HIV, patients with malignancies or transplant recipients, resulting in life-threatening diseases [1][2][3].Both innate and adaptive immune responses are essential to induce protection against fungi. Dendritic cells (DC) play a central role in the adaptive immune response by capturing fungi and presenting their antigens in major histocompatibility complex (MHC) class I and MHC class II molecules to T cells [4, 5]. DC express a panel of microbial recognition receptors such as Toll-like receptors (TLR) and C-type lectin receptors that are essential for the elicitation of adaptive immune responses [6]. Of these receptors, TLR2 and the DCassociated C-type lectin (dectin-1) are specifically involved in recognition of fungal components [7][8][9]. Zymosan and fungal pathogens like C. albicans and A. fumigatus are sensed by TLR2 that signals via myeloid differentiation factor 88 (MyD88), resulting in NF-jB activation and the production of cytokines [10][11][12][13]. The importance of this signaling cascade can be inferred from the fact that MyD88-knockout mice show an increased susceptibility to fungal infections [14,15].Dectin-1 is expressed on myeloid cells like macrophages, neutrophils, monocytes, and even a subset of T cells [16]. Dectin-1 mediates fungal recognition and Revised 2/11/07 Accepted 11/12/07 [DOI 10.1002/eji.200737647] Key words: Antigen presentation Á Dendritic cell Á Fungal Á T cell Abbreviations: b2m: b2-microglobulin Á Dectin-1: DC-associated C-type lectin-1 Á CR3: complement receptor 3 Á MR: mannose receptor Á SIGNR1: ICAM-3-grabbing nonintegrin (DC-SIGN) homolog, SIGN-related...

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Section: Discussionmentioning

confidence: 99%

CD8^– dendritic cells preferentially cross‐present Saccharomyces cerevisiae antigens

et al. 2008

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“…In addition, diseases of the lung (lymphocytic interstitial pneumonitis), heart (myocytolysis and myocarditis), and kidney (tubulointerstitial nephritis, segmental glomerulosclerosis, and microcystic dilatation) develop in these Tg mice (19,24). Mucosal Candida infection in these Tg mice closely mimics the clinical and pathological features of candidal infection in human HIV infection (18,25) and has allowed us to perform controlled studies on the immunopathogenesis of mucosal candidiasis in HIV infection (26)(27)(28).…”

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Altered Immune Response Differentially Enhances Susceptibility to Cryptococcus neoformans and Cryptococcus gattii Infection in Mice Expressing the HIV-1 Transgene

et al. 2013

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e Cryptococcus neoformans var. grubii is the most frequent cause of AIDS-associated cryptococcosis worldwide, while Cryptococcus gattii usually infects immunocompetent people. To understand the mechanisms which cause differential susceptibility to these cryptococcal species in HIV infection, we established and characterized a model of cryptococcosis in CD4C/HIV MutA transgenic (Tg) mice expressing gene products of HIV-1 and developing an AIDS-like disease. Tg mice infected intranasally with C. neoformans var. grubii strain H99 or C23 consistently displayed reduced survival compared to non-Tg mice at three graded inocula, while shortened survival of Tg mice infected with C. gattii strain R265 or R272 was restricted to a single high inoculum. HIV-1 transgene expression selectively augmented systemic dissemination to the liver and spleen for strains H99 and C23 but not strains R265 and R272. Histopathologic examination of lungs of Tg mice revealed large numbers of widely scattered H99 cells, with a minimal inflammatory cell response, while in the non-Tg mice H99 was almost completely embedded within extensive mixed inflammatory cell infiltrates. In contrast to H99, R265 was dispersed throughout the lung parenchyma and failed to induce a strong inflammatory response in both Tg and non-Tg mice. HIV-1 transgene expression reduced pulmonary production of CCL2 and CCL5 after infection with H99 or R265, and production of these two chemokines was lower after infection with R265. These results indicate that an altered immune response in these Tg mice markedly enhances C. neoformans but not C. gattii infection. This model therefore provides a powerful new tool to further investigate the immunopathogenesis of cryptococcosis.

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“…We have previously shown that PMNs from these Tg mice are quantitatively and functionally intact and that depletion of PMNs does not alter oral or gastrointestinal burdens of C. albicans or cause systemic dissemination of endogenous (gastrointestinal) origin (42). However, interference with both on May 11, 2018 by guest http://iai.asm.org/ macrophage and PMN functions was necessary to enhance the susceptibility of T-and B-cell-deficient SCID mice to orogastric candidiasis (33).…”

Section: Discussionmentioning

confidence: 96%

“…Fisher's exact test was utilized to compare the proportions of surviving animals at the conclusion of the observation period. Oral burdens of C. albicans were compared as described previously (14,37,42). A pairwise fixed reallocation randomization test (60) was used to analyze gene expression results in real-time qRT-PCR.…”

Section: Vol 77 2009 Response To C Albicans In Hiv Gene-expressingmentioning

confidence: 99%

“…Using a model of mucosal Candida infection in transgenic (Tg) mice expressing HIV-1 Nef in CD4 ϩ T cells, dendritic cells, and macrophages which closely mimics the clinical and pathological features of candidal infection in human HIV infection (14), we have previously shown that altered CD4 ϩ T-cell phenotype and function determine the susceptibility to chronic carriage of C. albicans in these Tg mice (37). However, PMNs from the Tg mice were unimpaired in their capacity to produce an oxidative burst and to phagocytose and kill C. albicans in vitro, and depletion of PMNs in these Tg mice did not alter the oral or gastrointestinal burdens of C. albicans or cause systemic dissemination (42). Accordingly, the defective anti-Candida effector mechanisms that render these Tg mice susceptible to mucosal candidiasis have not yet been identified.…”

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Macrophage-Mediated Responses toCandida albicansin Mice Expressing the Human Immunodeficiency Virus Type 1 Transgene

Goupil¹,

Trudelle²,

Dugas³

et al. 2009

Infect Immun

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The critical impairments of innate and adaptive immunity that cause susceptibility to mucosal candidiasis in human immunodeficiency virus (HIV) infection have not been fully determined. We therefore conducted an analysis of macrophage-mediated responses to Candida albicans in transgenic (Tg) mice expressing Nef, Env, and Rev of HIV type 1 (HIV-1) in CD4 ؉ T cells, dendritic cells, and macrophages and developing an AIDS-like disease (CD4C/HIV MutA Tg mice). Macrophages were successfully recruited to the oral and gastric mucosae of these Tg mice in response to chronic carriage of C. albicans and displayed polarization toward an alternatively activated phenotype. Functionally, peritoneal macrophages from uninfected Tg mice exhibited increased phagocytosis of C. albicans and enhanced production of interleukin 6 and monocyte chemoattractant protein 1, demonstrating that the HIV-1 transgene independently activates selected macrophage functions. Production of H 2 O 2 by macrophages from Tg mice primed with gamma interferon and treated with phorbol 12-myristate 13-acetate or C. albicans was moderately reduced, but expression of the HIV-1 transgene did not alter production of nitric oxide or reduce killing of C. albicans. A knockout of the inducible nitric oxide synthase (NOS2) gene in these Tg mice did not augment oral or gastrointestinal burdens during chronic carriage of C. albicans or cause systemic dissemination, likely due to a redundancy provided by partially preserved production of H 2 O 2 and oxygen-independent candidacidal mechanisms. Thus, the macrophage response to C. albicans is largely preserved in these Tg mice, and no functional macrophage defect appears to primarily determine the susceptibility to mucosal candidiasis.

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CD8⁺T Cells but Not Polymorphonuclear Leukocytes Are Required To Limit Chronic Oral Carriage ofCandida albicansin Transgenic Mice Expressing Human Immunodeficiency Virus Type 1

Cited by 32 publications

References 50 publications

CD8^– dendritic cells preferentially cross‐present Saccharomyces cerevisiae antigens

CD8^– dendritic cells preferentially cross‐present Saccharomyces cerevisiae antigens

Altered Immune Response Differentially Enhances Susceptibility to Cryptococcus neoformans and Cryptococcus gattii Infection in Mice Expressing the HIV-1 Transgene

Macrophage-Mediated Responses toCandida albicansin Mice Expressing the Human Immunodeficiency Virus Type 1 Transgene

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CD8+T Cells but Not Polymorphonuclear Leukocytes Are Required To Limit Chronic Oral Carriage ofCandida albicansin Transgenic Mice Expressing Human Immunodeficiency Virus Type 1

Cited by 32 publications

References 50 publications

CD8– dendritic cells preferentially cross‐present Saccharomyces cerevisiae antigens

CD8– dendritic cells preferentially cross‐present Saccharomyces cerevisiae antigens

Altered Immune Response Differentially Enhances Susceptibility to Cryptococcus neoformans and Cryptococcus gattii Infection in Mice Expressing the HIV-1 Transgene

Macrophage-Mediated Responses toCandida albicansin Mice Expressing the Human Immunodeficiency Virus Type 1 Transgene

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CD8⁺T Cells but Not Polymorphonuclear Leukocytes Are Required To Limit Chronic Oral Carriage ofCandida albicansin Transgenic Mice Expressing Human Immunodeficiency Virus Type 1

CD8^– dendritic cells preferentially cross‐present Saccharomyces cerevisiae antigens

CD8^– dendritic cells preferentially cross‐present Saccharomyces cerevisiae antigens