Sequential Dysfunction and Progressive Depletion of Candida albicans-Specific CD4 T Cell Response in HIV-1 Infection

Fengliang Liu, Xiuzhen Fan, Sarah Auclair, Monique Ferguson, Jiaren Sun, Lynn Soong, Wei Hou, Robert R. Redfield, Deborah L. Birx, Silvia Ratto-Kim, Merlin L. Robb, Jerome H. Kim, Nelson L. Michael, Haitao Hu

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10 Scopus citations

Abstract

Loss of immune control over opportunistic infections can occur at different stages of HIV-1 (HIV) disease, among which mucosal candidiasis caused by the fungal pathogen Candida albicans (C. albicans) is one of the early and common manifestations in HIV-infected human subjects. The underlying immunological basis is not well defined. We have previously shown that compared to cytomegalovirus (CMV)-specific CD4 cells, C. albicans-specific CD4 T cells are highly permissive to HIV in vitro. Here, based on an antiretroviral treatment (ART) naïve HIV infection cohort (RV21), we investigated longitudinally the impact of HIV on C. albicans- and CMV-specific CD4 T-cell immunity in vivo. We found a sequential dysfunction and preferential depletion for C. albicans-specific CD4 T cell response during progressive HIV infection. Compared to Th1 (IFN-γ, MIP-1β) functional subsets, the Th17 functional subsets (IL-17, IL-22) of C. albicans-specific CD4 T cells were more permissive to HIV in vitro and impaired earlier in HIV-infected subjects. Infection history analysis showed that C. albicans-specific CD4 T cells were more susceptible to HIV in vivo, harboring modestly but significantly higher levels of HIV DNA, than CMV-specific CD4 T cells. Longitudinal analysis of HIV-infected individuals with ongoing CD4 depletion demonstrated that C. albicans-specific CD4 T-cell response was preferentially and progressively depleted. Taken together, these data suggest a potential mechanism for earlier loss of immune control over mucosal candidiasis in HIV-infected patients and provide new insights into pathogen-specific immune failure in AIDS pathogenesis.

Original languageEnglish (US)
Article numbere1005663
JournalPLoS Pathogens
Volume12
Issue number6
DOIs
StatePublished - Jun 1 2016

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ASJC Scopus subject areas

  • Microbiology
  • Parasitology
  • Virology
  • Immunology
  • Genetics
  • Molecular Biology

Cite this

Liu, F., Fan, X., Auclair, S., Ferguson, M., Sun, J., Soong, L., Hou, W., Redfield, R. R., Birx, D. L., Ratto-Kim, S., Robb, M. L., Kim, J. H., Michael, N. L., & Hu, H. (2016). Sequential Dysfunction and Progressive Depletion of Candida albicans-Specific CD4 T Cell Response in HIV-1 Infection. PLoS Pathogens, 12(6), [e1005663]. https://doi.org/10.1371/journal.ppat.1005663