Mkp-1 deficiency strengthens immune defense against fungal infection

Abstract Fungal infections are a serious threat to people with compromised immune system. The recognition of fungal pathogens relies on pathways mediated by TLRs and C-type lectin receptors. Activation these TLR receptor converge both NF-κB MAPKs initiate cytokine chemokine production, leading phagocyte recruitment pathogen elimination. Mkp-1 is negative feedback regulator the p38 JNK MAPKs. To understand role in defense against pathogens, we assessed effects deficiency response C. albicans, most common pathogen. Contrary our previous observation E. coli or bacterial products such as LPS, Mkp1−/− mice were protected from lethal dose albicans. In albicans challenge, produced greater amounts TNF-α, had lower kidney burdens smaller lesions. wildtype large number neutrophils found kidneys, forming clusters surrounding contrast, far less kidneys Mkp-1−/− mice, although appeared express levels neutrophil elastase form tighter fungi. Upon stimulation heat-killed yeasts hyphae bone marrow-derived macrophages (BMDM) also TNF-α higher activities than did WT BMDM. production BMDM was attenuated pharmacological inhibitors MEK1, JNK, p38, Syk. Taken together, results suggest that during infection acts hamper pathogens. *The studies supported NIH grants (AI113930 AI124029 Y.L., AI121196 AI123253 J.Z.).