Lack of galectin-3 drives response to Paracoccidioides brasiliensis toward a Th2-biased immunity.
There is recent evidence that galectin-3 participates in immunity to infections, mostly by tuning cytokine production. We studied the balance of Th1/Th2 responses to P. brasiliensis experimental infection in the absence of galectin-3. The intermediate resistance to the fungal infection presented by C57BL/6 mice, associated with the development of a mixed type of immunity, was replaced with susceptibility to infection and a Th2-polarized immune response, in galectin-3-deficient (gal3(-/-)) mice. Such a response was associated with defective inflammatory and delayed type hypersensitivity (DTH) reactions, high IL-4 and GATA-3 expression and low nitric oxide production in the organs of infected animals. Gal3(-/-) macrophages exhibited higher TLR2 transcript levels and IL-10 production compared to wild-type macrophages after stimulation with P. brasiliensis antigens. We hypothesize that, during an in vivo P. brasiliensis infection, galectin-3 exerts its tuning role on immunity by interfering with the generation of regulatory macrophages, thus hindering the consequent Th2-polarized type of response.
Ruas
Luciana Pereira
LP
Departamento de Biologia Celular e Molecular e Bioagentes Patogênicos, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, Brasil.
Bernardes
Emerson Soares
ES
Fermino
Marise Lopes
ML
de Oliveira
Leandro Licursi
LL
Hsu
Daniel K
DK
Liu
Fu-Tong
FT
Chammas
Roger
R
Roque-Barreira
Maria-Cristina
MC
D000818:Animals; D050990:GATA3 Transcription Factor / Q000032:analysis; D037502:Galectin 3 / Q000172:deficiency* / Q000276:immunology; D007111:Immunity, Cellular; D016753:Interleukin-10 / Q000032:analysis; D015847:Interleukin-4 / Q000032:analysis; D008264:Macrophages / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009569:Nitric Oxide / Q000032:analysis; D010228:Paracoccidioides / Q000276:immunology*; D010229:Paracoccidioidomycosis / Q000276:immunology; D012333:RNA, Messenger / Q000032:analysis; D018418:Th2 Cells / Q000276:immunology*; D051195:Toll-Like Receptor 2 / Q000235:genetics
D050990:GATA3 Transcription Factor; D037502:Galectin 3; D012333:RNA, Messenger; D051195:Toll-Like Receptor 2; D016753:Interleukin-10; D015847:Interleukin-4; D009569:Nitric Oxide