title: Susceptibility of TLR4-defective C3H/HeJ mice to Coccidioides posadasii infection.
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.
authors.affiliation: Department of Microbiology and Immunology, University of Texas Health Science Center, San Antonio, Texas, USA. Shanjana-Awasthi@ouhsc.edu
authors.forename: Shanjana
authors.initials: S
authors.lastname: Awasthi
mesh_terms: D000818:Animals; D000908:Antibodies, Fungal / Q000097:blood; D003045:Coccidioides / Q000276:immunology* / Q000472:pathogenicity; D003047:Coccidioidomycosis / Q000235:genetics / Q000276:immunology*; D015169:Colony Count, Microbial; D003713:Dendritic Cells / Q000276:immunology; D004198:Disease Susceptibility; D005260:Female; D018664:Interleukin-12 / Q000378:metabolism; D051379:Mice; D008809:Mice, Inbred C3H; D018345:Mice, Knockout; D013154:Spleen / Q000382:microbiology; D016019:Survival Analysis; D051197:Toll-Like Receptor 4 / Q000172:deficiency*
chemical_list: D000908:Antibodies, Fungal; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D018664:Interleukin-12