Contributions of the MyD88-dependent receptors IL-18R, IL-1R, and TLR9 to host defenses following pulmonary challenge with Cryptococcus neoformans

PLoS One. 2011;6(10):e26232. doi: 10.1371/journal.pone.0026232. Epub 2011 Oct 19.

Abstract

Signaling via the adapter protein, MyD88, is important in the host defense against Cryptococcus neoformans infection. While certain Toll-like receptors (TLRs) can enhance the clearance of Cryptococcus, the contributions of MyD88-dependent, TLR-independent pathways have not been fully investigated. We examined the roles of IL-1R and IL-18R in vivo by challenging C57BL/6 mice with a lethal strain of Cryptococcus. We found that the absence of IL-18R, but not IL-1R, causes a shift in the survival curve following pulmonary delivery of a virulent strain of C. neoformans (H99). Specifically, IL-18R-deficient mice have significantly shorter median survival times compared to wild-type mice following infection. Cytokine analysis of lung homogenates revealed that deficiency of IL-IR, IL-18R, or MyD88 is associated with diminished lung levels of IL-1β. In order to compare these findings with those related to TLR-deficiency, we studied the effects of TLR9-deficiency and found that deficiency of TLR9 also affects the survival curve of mice following challenge with C. neoformans. Yet the lungs from infected TLR9-deficient mice have robust levels of IL-1β. In summary, we found that multiple signaling components can contribute the MyD88-dependent host responses to cryptococcal infection in vivo and each drives distinct pulmonary responses.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Cryptococcus neoformans / physiology*
  • Mice
  • Mice, Knockout
  • Myeloid Differentiation Factor 88 / physiology*
  • Receptors, Interleukin-1 / physiology*
  • Receptors, Interleukin-18 / physiology*
  • Toll-Like Receptor 9 / physiology*

Substances

  • Myeloid Differentiation Factor 88
  • Receptors, Interleukin-1
  • Receptors, Interleukin-18
  • Toll-Like Receptor 9