Lack of Galectin-3 Drives Response to Paracoccidioides brasiliensis toward a Th2-Biased Immunity

Abstract

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.

Dendritic cell interactions withHistoplasmaandParacoccidioides

“…73 Gal-3 has a known role in atopic dermatitis and asthma by promoting an anti-inflammatory Th2 response, while it diminishes the Th2 response in Paracoccidioides infection by negatively regulating IL-10 production. 74 Gal-3 affects Th1, 75 Th2, 74 and Th17 responses, 76 depending on the infecting pathogen. Presumably, this is dependent on the type of receptors involved and their interaction with the stimulant.…”

Association between circulating galectin-3 levels and the immunological, inflammatory and nutritional parameters in patients with colorectal cancer

“…Galectin-3 also has a role as an immunological modulator by regulating cytokine production, phagocytosis, chemotaxis and apoptosis induction (8)(9)(10)(11)(12). As for cytokine production, galectin-3 has been reported to have inhibitory effects on interleukin-12 (IL-12) production by dendritic cells (9).…”

“…As for cytokine production, galectin-3 has been reported to have inhibitory effects on interleukin-12 (IL-12) production by dendritic cells (9). Macrophages from galectin-3 deficient mice produce higher amounts of IL-10 compared with those from wild-type mice (11). The production of IL-6 has been reported to be influenced by galectin-3 through the tumor-producing galectin-3 binding protein (13).…”

Galectin-3 Negatively Regulates Dendritic Cell Production of IL-23/IL-17–Axis Cytokines in Infection by Histoplasma capsulatum

“…Also by inhibiting IL-12 production, gal3 promotes the Th2 response in mouse models of atopic dermatitis and asthma (8,9). In contrast, gal3 suppresses the Th2 response in infection by Paracoccidioides brasiliensis (10). Interestingly, gal3 also suppresses the regulatory T cell response through downregulating IL-10 release by DCs and, thus, induces Th1/Th17 responses to aggravate experimental autoimmune encephalomyelitis (EAE) (11).…”