Trypanosoma Cruzi Sensitizes Mice to Fulminant Seb-Induced Shock: Overrelease of Inflammatory Cytokines and Independence of Chagas' Disease or TCR V??-Usage

Abstract

Trypanosoma cruzi-infected mice display increased susceptibility to shock induced by injection of lipopolysaccharide (LPS), anti-CD3, or resulting from interleukin (IL)-10-defective response to the parasite itself, but the basis of such susceptibility remains unknown. Herein, we tested the susceptibility of mice inoculated with virulent and avirulent T. cruzi to staphylococcal enterotoxins (SE), potent inducers of inflammatory cytokine secretion. Mice infected with T. cruzi CL-strain or inoculated with the avirulent clone CL-14, a clone that does not induce disease or polyclonal lymphocyte activation, succumb suddenly to low doses of staphylococcal enterotoxin B (SEB), but not to staphylococcal enterotoxin A (SEA). High plasma levels of TNF, IFN-gamma, and liver transaminases alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were found in these mice, indicating lethal toxic shock. Sensitization to shock required inoculation of live avirulent trypomastigotes and a time interval before challenge with SEB. We found no prior skewing of T cell receptor (TCR) Vbeta-repertoire in CL-14-inoculated mice that could be responsible for sensitization. Splenocytes from CL-14-inoculated mice proliferated more under anti-Vbeta8 than anti-TCRbeta stimulation when compared with normal mice, but were suppressed to SEB stimulation. Both SEB and anti-Vbeta8 antibodies stimulated splenocytes from T. cruzi-inoculated mice to secrete higher levels of inflammatory cytokines than normal controls. Taken together, our results show that T. cruzi inoculation can sensitize mice to lethal SEB-induced shock even in the absence of tissue damage, polyclonal lymphocyte activation, or previously increased levels of inflammatory cytokines, and they suggest that altered reactivity of Vbeta8 lymphocytes may be involved in the phenomenon.

Pharmacological Inhibition of Transforming Growth Factor β Signaling Decreases Infection and Prevents Heart Damage in Acute Chagas' Disease

“…Swiss mice infected with the Y strain of T. cruzi usually die on May 9, 2018 by guest http://aac.asm.org/ between 18 and 21 days postinfection, as a result of a complex host-parasite interplay involving inflammation, systemic activation of the natural and acquired immune responses, progressive renal and heart dysfunctions, and eventually systemic shock (20). We found that pharmacological treatment of T. cruzi-infected mice with a single dose of 10 mg/kg SB-431542 given on day 3 postinfection led to improved survival rates compared to untreated animals and that this difference was significant at 20 dpi.…”

Staphylococcal enterotoxin B administration in pregnant rats alters the splenic lymphocyte response in adult offspring rats

“…The immune response of T cells to SEB displays a biphasic change [5, 6] which consists of an early activation presented as T cell proliferation and a second anergy due to apoptosis of the appropriate T cells. Ultimately, the hyper-response and immunosuppression of T cells following SEB exposure may lead to illness and disease in mammals [7, 8]. A variety of literatures [9–12] have demonstrated the influence of SEB exposure on T cells during adulthood or neonatal period in animal experiments.…”

The staphylococcal enterotoxin (SE) family

“…Mice have historically been used by various groups as an alternative to monkeys for studying superantigen-mediated effects in vivo 79 - 88 . From a cost perspective, mice are very feasible for basic toxin studies and discovery of therapeutics/vaccines for combating staphylococcal superantigen-induced shock.…”

“…Additionally, mice are naturally less susceptible (vs. monkeys) to SEs and TSST-1 because of decreased affinity for MHC II 81 , 84 . Therefore, potentiating agents such as d -galactosamine, actinomycin D, lipopolysaccharide (LPS), viruses, or even protozoa are used by various groups with different mouse strains 80 - 83 , 87 , 88 . These agents amplify SE or TSST-1 effects in mice so that practical, lower amounts of these protein toxins elicit a quantifiable form of toxic shock (i.e., lethality or temperature change) useful for therapeutic and vaccine discovery.…”