Furthermore, BMDC treated with rHp-CPI before ovalbumin (OVA) antigen pulsing induced a weaker proliferation response and less interferon-γ production of OVA-specific CD4+ T cells compared with BMDC without rHp-CPI pre-treatment. Adoptive transfer of rHp-CPI-treated and OVA-loaded

BMDC to mice induced significantly lower levels of antigen-specific antibody response than the BMDC loaded with antigen alone. These results demonstrated that the CPI from nematode parasites is able to modulate differentiation and activation stages of BMDC. It also interferes with antigen and MHC-II molecule Antiinfection Compound Library in vitro processing and Toll-like receptor signalling pathway, resulting in functionally deficient DC that induce a suboptimum immune response. Nematode parasite infections are common in many parts of the world and cause significant health problems in humans.[1] Infections with this group of pathogens often undergo a chronic and asymptomatic course and induce a T helper type 2-dominated immune response.[2, 3] In addition, nematode infections often induce immunosuppression, which is believed to be an important strategy for the BVD-523 manufacturer survival of the parasite in the host.[4, 5] The immunosuppression associated with nematode infection is also demonstrated as the suppression of immune responses to unrelated

antigens and immune protection against concurrent infection with other pathogens.[6, 7] Epidemiological studies showed that helminth infections in human populations are also associated with decreased prevalence of autoimmune disorders and allergic diseases (hygiene hypothesis).[8, 9] Although nematode infections are known to elicit T helper type 2-dominant immune responses, which are required for immune protection against the nematode pathogens,[10] many

studies show that these pathogens also induce a regulatory T-cell response and cytokines that mediate the immunosuppression.[11-13] Carbohydrate In mice infected with the murine nematode parasite, Heligmosomoides polygyrus, we identified a subset of dendritic cells (DC) that are selectively expanded following H. polygyrus infection and induce interleukin-10 (IL-10) production by T cells and FoxP3+ CD4+ T-cell response.[14] Previous studies with H. polygyrus and other nematode species also demonstrated that the crude preparation or excretory–secretory (ES) products from the parasites are able to modulate the phenotypes and functions of immune cells.[15-17] It has been reported that the ES products from H. polygyrus can modulate the antigen presentation function of DC and specifically induce an IL-10-producing T-cell response.[15] However, the immunoregulatory molecule(s) produced by H. polygyrus have not been fully characterized. A number of studies in recent years have shown that cysteine proteases inhibitor (CPI; cystatin) is one of the major immune modulators produced by nematode parasites.