Medical College of Wisconsin
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Th17 cells confer long-term adaptive immunity to oral mucosal Candida albicans infections. Mucosal Immunol 2013 Sep;6(5):900-10

Date

12/20/2012

Pubmed ID

23250275

Pubmed Central ID

PMC3608691

DOI

10.1038/mi.2012.128

Scopus ID

2-s2.0-84883176275 (requires institutional sign-in at Scopus site)   164 Citations

Abstract

Oropharyngeal candidiasis (OPC) is an opportunistic infection caused by Candida albicans. Despite its prevalence, little is known about C. albicans-specific immunity in the oral mucosa. Vaccines against Candida generate both T helper type 1 (Th1) and Th17 responses, and considerable evidence implicates interleukin (IL)-17 in immunity to OPC. However, IL-17 is also produced by innate immune cells that are remarkably similar to Th17 cells, expressing the same markers and localizing to similar mucosal sites. To date, the relative contribution(s) of Th1, Th17, and innate IL-17-producing cells in OPC have not been clearly defined. Here, we sought to determine the nature and function of adaptive T-cell responses to OPC, using a new recall infection model. Mice subjected to infection and re-challenge with Candida mounted a robust and stable antigen-specific IL-17 response in CD4+ but not CD8+ T cells. There was little evidence for Th1 or Th1/Th17 responses. The Th17 response promoted accelerated fungal clearance, and Th17 cells could confer protection in Rag1-/- mice upon adoptive transfer. Surprisingly, CD4 deficiency did not cause OPC but was instead associated with compensatory IL-17 production by Tc17 and CD3+CD4-CD8- cells. Therefore, classic CD4+Th17 cells protect from OPC but can be compensated by other IL-17-producing cells in CD4-deficient hosts.

Author List

Hernández-Santos N, Huppler AR, Peterson AC, Khader SA, McKenna KC, Gaffen SL

Author

Anna Huppler MD Associate Professor in the Pediatrics department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Adaptive Immunity
Adoptive Transfer
Animals
Candida albicans
Candidiasis
Cells, Cultured
Disease Models, Animal
Humans
Immunity, Mucosal
Interleukin-17
Mice
Mice, Inbred C57BL
Mice, Knockout
Mouth Mucosa
Oropharynx
T-Lymphocyte Subsets
Th17 Cells