Interactions between TLR2, TLR4, and mannose receptors with gp43 fromParacoccidioides brasiliensisinduce cytokine production by human monocytes

Abstract

The glycoprotein gp43 is an immunodominant antigen secreted by Paracoccidioides brasiliensis, the agent of paracoccidioidomycosis. The present study evaluated whether gp43 can interact with toll-like (TLR2, TLR4) and mannose (MR) receptors on the surface of human monocytes, and how that affects their expression and cytokine production. Monocytes were incubated with or without monoclonal antibodies anti-TLR2, anti-TLR4, or anti-MR, individually or in combination, prior to the addition of gp43. The gp43 binding to monocyte surface, as well as expression of TLR2, TLR4, and MRs were analyzed by flow cytometry, while production of TNF-α and IL-10 was monitored by ELISA. The results suggested that gp43 binds to TLR2, TLR4, and MR receptors, with TLR2 and MR having the strongest effect. All three receptors influenced the production of IL-10, while TNF-α production was associated with expression of TLR4 and MR. The modulatory effect of gp43 was demonstrated by high levels of TLR4 expression associated with increased production of TNF-α after 4 h of culture. Alternatively, high levels of TLR2 expression, and elevated production of IL-10, were detected after 18 h. We showed that interaction between gp43 and monocytes may affect the innate immune response by modulating the expression of the pattern recognition receptors TLR2, TLR4 and MR, as well as production of pro- and anti-inflammatory cytokines.

Mannosyl-Recognizing Receptors Induce an M1-Like Phenotype in Macrophages of Susceptible Mice but an M2-Like Phenotype in Mice Resistant to a Fungal Infection

“…CR3 and MR recognize P. brasiliensis conidia [30], while gp43, the immunodominant antigen of P. brasiliensis , was shown to bind to the MRs and inhibit the phagocytic and fungicidal ability of peritoneal macrophages from susceptible and resistant mice [31]. Two recent studies with human monocytes have also suggested that MR, TLR2, TLR4, and dectin-1 contribute to the recognition of gp43 and P. brasiliensis yeasts, indicating important roles for these pathogen receptors in the immune response against the fungus [32], [33].…”

Characterization of functional mannose receptor in a continuous hybridoma cell line

“…Macrophages are found in virtually all tissues and are among the first cells to encounter an invading microorganism. The recognition capacity of the MR is broad allowing for the capture and uptake of a variety of pathogens including Paracoccidioides brasiliensis [26,27] Candida albicans [28], Leishmania donovani [29], Mycobacterium tuberculosis [30,31], Pneumocystis jirovecii ( formally Pneumocystis carinii sp . hominis ) [32], Klebsiella pneumoniae [33], HIV [11,34], Dengue [35], Hepatitis B [36], and influenza A [10,37].…”

Dendritic cell interactions withHistoplasmaandParacoccidioides

“…The authors concluded that P. brasiliensis could be phagocytosed by the use of mannose and dectin-1 receptors, 100 as proposed in previous studies. [101][102][103] By studying the predominant DC and associated cytokine types, Pina et al explored other mechanisms that could explain the resistance and susceptibility of mice to infection. In their study, Pina et al found that when infected with P. brasiliensis, there was a predominance of myeloid bone marrow DCs in susceptible (B10.A) mice and plasmacytoid DCs in resistant (A/J) mice.…”