Abstract
The current studies evaluated the role of interleukin (IL)-17A in the induction of protective immunity against pulmonary cryptococcosis in mice. Protection against pulmonary infection with C. neoformans strain H99γ was associated with increased IL-17A production. Signaling through the IFN-γ receptor (R) was required for increased IL-17A production, however, a Th17-type cytokine profile was not observed. Neutrophils were found to be the predominant leukocytic source of IL-17A, rather than T cells, suggesting that the IL-17A produced was not part of a T cell-mediated Th17-type immune response. Depletion of IL-17A in mice during pulmonary infection with C. neoformans strain H99γ resulted in an initial increase in pulmonary fungal burden, but had no effect on cryptococcal burden at later time points. Also, depletion of IL-17A did not affect the local production of other cytokines. IL-17RA−/− mice infected with C. neoformans strain H99γ survived the primary infection as well as a secondary challenge with wild-type cryptococci. However, dissemination of the wild-type strain to the brain was noted in the surviving IL-17RA−/− mice. Altogether, our results suggested that IL-17A may be important for optimal protective immune responsiveness during pulmonary C. neoformans infection, but protective Th1-type immune responses are sufficient for protection against cryptococcal infection.
Highlights
Cryptococcus neoformans is an opportunistic fungal pathogen that causes pneumonia as well as life-threatening meningoencephalitis in individuals with T cell immune deficiencies [1,2,3,4,5]
Previous studies in our laboratory have shown that infection with an IFN-c-producing C. neoformans strain, H99c, results in a significant increase in pulmonary IL-17A cytokine production on day 7 post-inoculation compared to mice infected with the parental C. neoformans strain H99 [14,16]
We determined the expression of cytokines associated with the induction of Th17cytokine responses (IL-6, IL-17A, IL-21, IL-23, and TGF-b) in total lung homogenates derived from mice infected with wild-type C. neoformans strain H99 or the transgenic C. neoformans strain H99c on day 7 post-inoculation
Summary
Cryptococcus neoformans is an opportunistic fungal pathogen that causes pneumonia as well as life-threatening meningoencephalitis in individuals with T cell immune deficiencies [1,2,3,4,5]. Previous studies have shown that protective immunity against this organism is dependent upon the induction of Th1-type cytokine responses [3,5,6,7,8,9,10,11,12,13,14,15,16]. Additional studies have shown that increased IL17A production is associated with reduced cryptococcal burden [14,16,17], suggesting that IL-17A has a significant role in the generation of protective anti-cryptococcal immune responses. IL-17A is a proinflammatory cytokine produced by a subset of CD4+ T cells, termed Th17 cells (reviewed in [18,19,20]). IL-17A can elicit the production of G-CSF and KC (CXCL1), which both can induce neutrophil chemotaxis [21,31,32]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
