T. brucei infections abrogate diverse plasma cell-mediated effector B cell responses, independently of their specificity, affinity and host genetic background

Abstract

Antibody-mediated parasite killing is considered the most effective host immune response against extracellular trypanosome parasites. However, due to host-parasite co-evolution pressure, these parasites have “learned” how to hijack the host immune system via the development of immune evasion strategies. Hereby they prevent elimination and promote transmission. In the past, our group has shown that African trypanosome parasites are able to “shut down” the host B cell compartment, via the abolishment of the homeostatic B cell compartment. In line with this, we have reported that trypanosome infections result in detrimental outcomes on auto-reactive and cancer B cells. To unravel the immune mechanisms involved in these processes we adopted here a well-defined B cell vaccine model, i.e. the thymo-dependent hapten-carrier NP-CGG (4-Hydroxy-3-nitrophenylacetyl-Chicken Gamma Globulin) emulsified in Alum adjuvant. Results show that T. brucei infections abrogate the circulating titres of vaccine-induced CGG-specific as well as NP-specific IgG1+ antibodies, a hallmark of memory B cell responses in this model. This happens independently of their affinity and IFNɣ signalling. Next, we demonstrate that T. brucei infections also induce a decrease of anti-NP IgG3+ antibodies induced by the administration of NP coupled to Ficoll, a thymo-independent antigen. Confirming the non-specificity of the infection-associated immunopathology, this report also shows that trypanosome infections abolish vaccine-induced memory response against malaria parasite in BALB/c mice. Together, these data indicates that T. brucei infections impair every stages of B cell development, including effector plasma B cells, independently of their specificity and affinity as well as the host genetic background. African trypanosomiasis is a fatal infectious disease caused by an extracellular parasite of the Trypanosoma brucei species affecting both human and livestock. The most effective immune response against this pathogen involves the production of antibodies by B cells. However, experimental trypanosomiasis model in mice has demonstrated that this parasite has evolved multiple immune evasion strategies targeting B cells. For instance, trypanosomes abolish homeostatic B cell development, the adaptive protective response against unrelated antigens as well as the progression of B-cell mediated arthritis and multiple myeloma. Here, we demonstrate that infection of resistant C57BL/6 mice impairs the development of both thymo-dependent and -independent humoral response using the well-characterized hapten-carrier NP-CGG (4-Hydroxy-3-nitrophenylacetyl-Chicken Gamma Globulin) emulsified in Alum adjuvant and NP-Ficoll models, respectively. This occurs independently of antigen specific B cell affinity and the pro-inflammatory IFNɣ cytokine signalling. Finally, trypanosoma abolishes the vaccine-induced memory response against another life-threatening parasite, namely malaria, in Trypanosoma brucei susceptible BALB/c mice. In summary, African trypanosomiasis abrogates diverse plasma cell-mediated effector B cell responses, independently of their specificity, affinity and host genetic background.