Author(s): Awasthi S
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Abstract Coccidioides posadasii is one of the two fungal pathogens that cause coccidioidomycosis. The inhalation of air-borne arthroconidia leads to the formation of endospore-forming spherules in the lungs and pulmonary infection. In severe condition, the endospores are disseminated to other non-pulmonary organs in the body. The Toll-like receptors (TLR) expressed by a number of immune and non-immune cells can significantly impact the host defense and susceptibility to C. posadasii infection. In this study, we infected TLR4-defective C3H/HeJ mice with a sublethal dose of C. posadasii and studied fungal dissemination, mortality and humoral response. We also measured IL-12 cytokine secreted by C. posadasii-infected dendritic cells. We found that the C3H/HeJ mice were equally susceptible to C. posadasii as compared to C3H/OuJ mice which have intact TLR4. No significant changes were observed in pulmonary fungal load, survival and humoral response. The blockade of TLR4 did not affect C. posadasii-induced IL-12 secretion. However, the fungal counts were 10 times less in spleens of C3H/HeJ mice as compared to C3H/OuJ mice (P<0.05). Our results suggest that the TLR4 may not be involved in inducing protective host defense against C. posadasii, but it appears to be critical for fungal dissemination.
This article was published in Med Mycol
and referenced in Journal of Clinical & Cellular Immunology