Figure 1: Interaction of PRRs and coccidioidal components.
Surface Toll-like receptors (TLRs) as well as other C-type lectins [e.g. Dectin-1 and mannose receptor (MR) and pulmonary surfactant proteins (SP)-A and –D (SPD)] participate in the recognition of coccidioidal components or PAMPs (e.g. β-glucan, mannan and other unknown components). In coccidioidal infection, interaction of fungal PAMPs with PRRs activates a signalling pathway which occurs at the level of the intracellular adaptor molecule myeloid differentiation primary-response protein 88 (MyD88). The participations of other adaptor molecules such as Toll/interleukin-1 receptor (TIR) domain-containing adaptor protein (TIRAP), MyD88-adaptor-like protein (Mal), TIR domain-containing adaptor-including interferon-β (TRIF) and transcription factors including nuclear factor-κB (NF-κB) and interferon regulatory factor (IRF) have not been studied and remain to be confirmed. TLR-mediated MyD88 signalling and Dectin-1 activation induce the expression of pro-inflammatory cytokines including TNF-α, MIP-2, IL-6, IL-10 and IL-12, thus driving the immune response.