4.6 Article

Vaccine protection by Cryptococcus neoformans Δsgl1 is mediated by γδ T cells via TLR2 signaling

Journal

MUCOSAL IMMUNOLOGY
Volume 15, Issue 6, Pages 1416-1430

Publisher

ELSEVIER SCIENCE INC
DOI: 10.1038/s41385-022-00570-3

Keywords

-

Categories

Funding

  1. National Institute of Health (NIH) [AI136934, AI116420, AI125770]
  2. Veterans Affairs (VA) Program [I01BX002924]
  3. Department of Defense (DOD) [PR190642]
  4. Research Career Scientist (RCS) Award [IK6 BX005386]
  5. Burroughs Welcome Investigator in Infectious Diseases

Ask authors/readers for more resources

The administration of the Cryptococcus neoformans Delta sgl1 mutant vaccine can protect mice from subsequent infection, even during CD4(+) T cell deficiency. IFN-gamma and IL-17A, produced by gamma delta T cells, play a crucial role in this protection mechanism. The interaction between sterylglucosides (SGs), GXM, and toll-like receptor 2 (TLR2) stimulates the production of IFN-gamma and IL-17A.
We previously reported that administration of Cryptococcus neoformans Delta sgl1 mutant vaccine, accumulating sterylglucosides (SGs) and having normal capsule (GXM), protects mice from a subsequent infection even during CD4(+) T cells deficiency, a condition commonly associated with cryptococcosis. Here, we studied the immune mechanism that confers host protection during CD4(+)T deficiency. Mice receiving Delta sgl1 vaccine produce IFN gamma and IL-17A during CD4(+) T (or CD8(+) T) deficiency, and protection was lost when either cytokine was neutralized. IFN gamma and/or IL-17A are produced by gamma delta T cells, and mice lacking these cells are no longer protected. Interestingly, ex vivo gamma delta T cells are highly stimulated in producing IFN gamma and/or IL-17A by Delta sgl1 vaccine, but this production was significantly decreased when cells were incubated with C. neoformans Delta cap59/Delta sgl1 mutant, accumulating SGs but lacking GXM. GXM modulates toll-like receptors (TLRs), including TLR2. Importantly, neither Delta sgl1 nor Delta cap59/Delta sgl1 stimulate IFN gamma or IL-17A production by ex vivo gamma delta T cells from TLR2(-/-) mice. Finally, TLR2(-/-) animals do not produce IL-17A in response to Delta sgl1 vaccine and were no longer protected from WT challenge. Our results suggest that SGs may act as adjuvants for GXM to stimulate gamma delta T cells in producing IFN gamma and IL-17A via TLR2, a mechanism that is still preserved upon CD4(+) T deficiency.

Authors

I am an author on this paper
Click your name to claim this paper and add it to your profile.

Reviews

Primary Rating

4.6
Not enough ratings

Secondary Ratings

Novelty
-
Significance
-
Scientific rigor
-
Rate this paper

Recommended

No Data Available
No Data Available