TLR2 Mediates Immunity to Experimental Cysticercosis

Abstract

Information concerning TLR-mediated antigen recognition and regulation of immune responses during helminth infections is scarce. TLR2 is a key molecule required for innate immunity and is involved in the recognition of a wide range of viruses, bacteria, fungi and parasites. Here, we evaluated the role of TLR2 in a Taenia crassiceps cysticercosis model. We compared the course of T. crassiceps infection in C57BL/6 TLR2 knockout mice (TLR2-/-) with that in wild type C57BL/6 (TLR2+/+) mice. In addition, we assessed serum antibody and cytokine profiles, splenic cellular responses and cytokine profiles and the recruitment of alternatively activated macrophages (AAMφs) to the site of the infection. Unlike wild type mice, TLR2-/- mice failed to produce significant levels of inflammatory cytokines in either the serum or the spleen during the first two weeks of Taenia infection. TLR2-/- mice developed a Th2-dominant immune response, whereas TLR2+/+ mice developed a Th1-dominant immune response after Taenia infection. The insufficient production of inflammatory cytokines at early time points and the lack of Th1-dominant adaptive immunity in TLR2-/- mice were associated with significantly elevated parasite burdens; in contrast, TLR2+/+ mice were resistant to infection. Furthermore, increased recruitment of AAMφs expressing PD-L1, PD-L2, OX40L and mannose receptor was observed in TLR2-/- mice. Collectively, these findings indicate that TLR2-dependent signaling pathways are involved in the recognition of T. crassiceps and in the subsequent activation of the innate immune system and production of inflammatory cytokines, which appear to be essential to limit infection during experimental cysticercosis.

Helminth‐excreted/secreted products are recognized by multiple receptors on DCs to block the TLR response and bias Th2 polarization in a cRAF dependent pathway

“…2 C ). Since TLR2 is involved in the resistance to T. crassiceps infection (23), TcES may include molecules that can bind TLR2. To test this hypothesis, we performed binding assays with TcES‐FITC using BMDCs and splenic CD11c + DCs from TLR2‐deficient mice.…”

Immunoregulation byTaenia crassicepsand Its Antigens

“…The treatment of STAT6 KO mice, which develop CAMs and are highly resistant to infection, with an iNOS inhibitor in vivo rendered these mice susceptible to T. crassiceps infection [52]. Similarly, deficiency in TLR2, which helps to induce pro-inflammatory responses in mice that are otherwise genetically resistant, rendered them highly susceptible to helminth infection [53]. In contrast, the early depletion of AAMs with clodronate-loaded liposomes in susceptible BALB/c mice reduced parasite loads by 90% [54].…”

“…Moreover, the stimulation of mice with CpG, a bacteria- and virus-derived agonist of TLR9, can augment protective immunity to the cestode [103], opening the possibility for a cross regulation of susceptibility between virus and T. crassiceps when coinfection exists. This possibility can be extended to bacterial, protozoan, helminth, and fungal coinfections, given the discovery that TLR2 is involved in mediating resistance to this parasite [53]. …”

The CD20 homolog Ms4a8a integrates pro‐ and anti‐inflammatory signals in novel M2‐like macrophages and is expressed in parasite infection

“…Activation of the innate immune response by Trypanosomes and Taenia is preferentially mediated by activation of pattern-recognition receptors, especially TLRs [16][17][18][19]. In this study, we could demonstrate that Ms4a8a expression in BMDMs in vitro was strictly dependent on the activation of TLRs (TLR2, TLR4, TLR7) in addition to the M2 mediators dexa/IL-4.…”