Engagement of Penicillium marneffei conidia with multiple pattern recognition receptors on human monocytes.
P. marneffei is a thermal dimorphic fungus which causes penicilliosis, an opportunistic infection in immunocompromised patients in South and Southeast Asia. Little is known about the innate immune response to P. marneffei infection. Therefore, the initial response of macrophages to P. marneffei conidia was evaluated by us. Adhesion between monocytes from healthy humans and fungal conidia was examined and found to be specifically inhibited by MAbs against PRR, such as MR, (TLR)1, TLR2, TLR4, TLR6, CD14, CD11a, CD11b, and CD18. To study the consequences of these interactions, cytokines were also examined by ELISA. Binding of P. marneffei conidia to monocytes was significantly inhibited, in a dose-dependent manner, by MAbs against MR, TLR1, TLR2, TLR4, TLR6, CD14, CD11b and CD18. When monocytes were co-cultured with the conidia, there was an increase in the amount of surface CD40 and CD86 expression, together with TNF-alpha and IL-1beta production, compared to unstimulated controls. In assays containing anti-TLR4 or anti-CD14 antibody, reduction in the amount of TNF-alpha released by monocytes stimulated with P. marneffei conidia was detected. In addition, it was found that production of TNF-alpha and IL-1beta from adherent peripheral blood monocytes was partially impaired when heat-inactivated autologous serum, in place of untreated autologous serum, was added to the assay. These results demonstrate that various PRR on human monocytes participate in the initial recognition of P. marneffei conidia, and the engagement of PRR could partly initiate proinflammatory cytokine production.
Srinoulprasert
Yuttana
Y
Department of Microbiology, Faculty of Science, Mahidol University, Rama VI Road, Bangkok 10400, Thailand.
Pongtanalert
Piyapong
P
Chawengkirttikul
Runglawan
R
Chaiyaroj
Sansanee C
SC
D001210:Asia, Southeastern; D002448:Cell Adhesion; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D053583:Interleukin-1beta / Q000378:metabolism; D009000:Monocytes / Q000382:microbiology*; D010407:Penicillium / Q000276:immunology*; D051192:Receptors, Pattern Recognition / Q000276:immunology*; D013172:Spores, Fungal / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D053583:Interleukin-1beta; D051192:Receptors, Pattern Recognition; D014409:Tumor Necrosis Factor-alpha