The macrophage galactose-type lectin-1 (MGL1) recognizes Taenia crassiceps antigens, triggers intracellular signaling, and is critical for resistance to this infection.

C-type lectins are multifunctional sugar-binding molecules expressed on dendritic cells (DCs) and macrophages that internalize antigens for processing and presentation. Macrophage galactose-type lectin 1 (MGL1) recognizes glycoconjugates expressing Lewis X structures which contain galactose residues, and it is selectively expressed on immature DCs and macrophages. Helminth parasites contain large amounts of glycosylated components, which play a role in the immune regulation induced by such infections. Macrophages from MGL1(-/-) mice showed less binding ability toward parasite antigens than their wild-type (WT) counterparts. Exposure of WT macrophages to T. crassiceps antigens triggered tyrosine phosphorylation signaling activity, which was diminished in MGL1(-/-) macrophages. Following T. crassiceps infection, MGL1(-/-) mice failed to produce significant levels of inflammatory cytokines early in the infection compared to WT mice. In contrast, MGL1(-/-) mice developed a Th2-dominant immune response that was associated with significantly higher parasite loads, whereas WT mice were resistant. Flow cytometry and RT-PCR analyses showed overexpression of the mannose receptors, IL-4Rα, PDL2, arginase-1, Ym1, and RELM-α on MGL1(-/-) macrophages. These studies indicate that MGL1 is involved in T. crassiceps recognition and subsequent innate immune activation and resistance.

Differential response of antigen presenting cells from susceptible and resistant strains of mice to Taenia crassiceps infection.

Antigen presenting cells (APCs) are critically involved in the interaction between pathogens and the host immune system. Here, we examined two different populations of APCs in mice that are susceptible (BALB/c) or resistant (C57BL/6) to Taenia crassiceps cysticercosis. Bone marrow-derived dendritic cells (BMDCs) from both strains of mice were exposed to T. crassiceps excreted/secreted antigens (TcES) and, at the same time, to the Toll-like receptor (TLR) ligand LPS. BMDCs from BALB/c mice underwent a partial maturation when incubated with TcES and displayed decreased responses to TLR-dependent stimuli associated with low CD80, CD86, CD40 and CCR7 expression and impaired IL-15 production. These BMDCs-induced impaired allogenic responses. In contrast, BMDCs from C57BL/6 mice displayed normal maturation and induced strong allogenic responses. Moreover, the exposure to TcES resulted in a lower production of IL-12 and TNF-alpha by LPS-activated DCs from BALB/c mice compared to C57BL/6 DCs. Three parameters of macrophage activation were assessed during Taenia infection: LPS+IFN-gamma-induced production of IL-12, TNF-alpha and nitric oxide (NO) in vitro; infection-induced markers for alternatively activated macrophages (Arginase-1, RELM-alpha, Ym-1 and TREM-2 expression) and suppressive activity. The maximum response to LPS+IFN-gamma-induced TNF-alpha, IL-12 and NO production by macrophages from both strains of mice occurred 2 wk post-infection. However, as infection progressed, the production of these molecules by BALB/c macrophages declined. While the BALB/c macrophages displayed impaired pro-inflammatory responses, these macrophages showed strong Arginase-1, Ym-1, RELM-alpha and TREM-2 expression. By contrast, C57BL/6 macrophages maintained a pro-inflammatory profile and low transcripts for alternative activation markers. Macrophages from T. crassiceps-infected BALB/c mice showed stronger suppressive activity than those from C57BL/6 mice. These findings suggest that APC activation at both early and late time points during T. crassiceps infection is a possible mechanism that underlies the differential susceptibility to T. crassiceps infection displayed by these mouse strains.