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 IFNγ 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.

COVID-19 and Diarylamidines: The Parasitic Connection

“…Interestingly, DIZE treatment restored the clinical signs of the disease, with authors attributing the reversal to the restoration of specific autoimmune antibody levels. However, a recent study by the same group showed that DIZE treatment did not restore the thymo-dependent and independent humoral response or the vaccine-induced memory response (antibody levels) in malaria-vaccinated C57BL/6 mice following T. brucei infection [ 133 ]. Moreover, the authors proposed that vaccine memory was partially destroyed or the accessibility to those memories was prohibited by infection, further highlighting the need for malaria vaccine trials in areas where trypanosomiasis is prevalent.…”