Trypanosoma cruzi antigen immunization induces a higher B cell survival in BALB/c mice, a susceptible strain, compared to C57BL/6 B lymphocytes, a resistant strain to cardiac autoimmunity

Abstract

Chagas disease, caused by Trypanosoma cruzi, is endemic in Latin America and represents the most common infectious myocarditis worldwide. Autoimmunity is one of the mechanisms contributing to its pathogenesis. Although the cellular interactions that promote this autoimmune response are still poorly understood, several studies have demonstrated a key role for B lymphocytes since they secrete antibodies, cytokines and present antigens. Recently, we reported that immunization with cruzipain, an immunodominant T. cruzi antigen, induces a higher activation state in B cells from BALB/c mice (susceptible to cardiac autoimmunity) than B lymphocytes from C57BL/6 (a resistant strain). Here, we focused on the study of B cell survival in both mouse strains after cruzipain immunization and demonstrated an increased survival rate of B cells from BALB/c compared to C57BL/6 mice. This phenomenon was associated with a decreased expression of Fas/FasL and an increased expression of anti-apoptotic Bcl-2/Bcl-xL proteins. With the purpose to gain more knowledge about the mechanisms involved, we found that IL-4 produced by BALB/c B cells played a key role in the survival in an autocrine way whereas the addition of this bioactive cytokine rescued C57BL/6 B lymphocytes from apoptosis. Our findings suggest that in the absence of infection, both enhanced B cell activation induced by the immunization with a single parasite antigen and insufficient negative regulation can potentially contribute to autoimmunity seen in cruzipain immune BALB/c mice.

Different peripheral neuroendocrine responses to Trypanosoma cruzi infection in mice lacking adaptive immunity

“…The innate immune system has the ability to sense pathogens via germ line–encoded pattern recognition receptors. These receptors recognize pathogen associated molecular patterns (PAMPs), conserved molecules shared by several microorganisms, including T. cruzi, and trigger the activation of host innate responses 2–4 . Adaptive immunity to T. cruzi has been well characterized, with critical involvement of CD4 + Th1 and CD8 + T cells that recognize T. cruzi –specific antigens 2 .…”

“…These receptors recognize pathogen associated molecular patterns (PAMPs), conserved molecules shared by several microorganisms, including T. cruzi, and trigger the activation of host innate responses. [2][3][4] Adaptive immunity to T. cruzi has been well characterized, with critical involvement of CD4 + Th1 and CD8 + T cells that recognize T. cruzispecific antigens. 2 However, it is still unknown to what extent the absence of adaptive immunity influences neuroendorine responses triggered by T. cruzi inoculation.…”

Physiology and Pathology of Infectious Diseases: The Autoimmune Hypothesis of Chagas Disease

“…Nevertheless, the divergence between low parasite load in the tissue and severity of the lesions observed during the chronic phase reinforces the hypothesis that other factors than the immune response developed against the parasite might be involved in the development of Chagas pathology [19]. In this context, humoral and cellular autoimmune mechanisms are developed during Chagas disease [20][21][22][23]. Autoimmune mechanisms triggered during infection by T. cruzi may occur after bystander activation, parasite-cardiomyocyte harm, or molecular mimicry [24].…”

Expression of cysteine proteinases and cystatins in parasites and use of cysteine proteinase inhibitors in parasitic diseases. Part III: Protozoa (3): Kinetoplastids

“…In CRZ immunization, increased survival rate of B cells with increased IL-4 production in BALB/c (susceptible to cardiac autoimmunity) compared to C57BL/6 mice (resistant), was observed. The investigators concluded that CRZ immunization contributed in increasing host autoimmunity [147] . The role of attenuated Salmonella enterica, as a delivery system, carrying plasmid encoding CRZ was investigated.…”