Abstract
Salivarian trypanosomes are extracellular parasites causing anthroponotic and zoonotic infections. Anti-parasite vaccination is considered the only sustainable method for global trypanosomosis control. Unfortunately, no single field applicable vaccine solution has been successful so far. The active destruction of the host’s adaptive immune system by trypanosomes is believed to contribute to this problem. Here, we show that Trypanosome brucei brucei infection results in the lasting obliteration of immunological memory, including vaccine-induced memory against non-related pathogens. Using the well-established DTPa vaccine model in combination with a T. b. brucei infection and a diminazene diaceturate anti-parasite treatment scheme, our results demonstrate that while the latter ensured full recovery from the T. b. brucei infection, it failed to restore an efficacious anti-B. pertussis vaccine recall response. The DTPa vaccine failure coincided with a shift in the IgG1/IgG2a anti-B. pertussis antibody ratio in favor of IgG2a, and a striking impact on all of the spleen immune cell populations. Interestingly, an increased plasma IFNγ level in DTPa-vaccinated trypanosome-infected mice coincided with a temporary antibody-independent improvement in early-stage trypanosomosis control. In conclusion, our results are the first to show that trypanosome-inflicted immune damage is not restored by successful anti-parasite treatment.
Highlights
Salivarian trypanosomes are extracellular flagellated single-cell eukaryotic parasites that are known to colonize the mammalian bloodstream and lymphatics as well as the brain.More recently, fat tissue was identified as a major parasite survival location [1]
The Diphtheria Tetanus Pertussis ‘acellular’ (DTPa) vaccine does offer adequate protection against B. pertussis, with lung colony forming units (CFUs) rapidly declining over a 9-day monitoring period (Figure 1B)
DTPa-vaccinated mice that had been exposed to the T. b. brucei infection eight weeks earlier, subsequently cured and allowed to recover for a 6-week period, completely failed to mount a protective vaccine recall response
Summary
Salivarian trypanosomes are extracellular flagellated single-cell eukaryotic parasites that are known to colonize the mammalian bloodstream and lymphatics as well as the brain.More recently, fat tissue was identified as a major parasite survival location [1]. Gambiense are the agents of sleeping sickness, i.e., human African trypanosomosis (HAT) [2]. The ‘AT’ classification of T. evansi has, been called into question, as this parasite has been reported as the causative agent of several cases of atypical human trypanosomosis (aHT) in Asia [7,8,9]. Tsetses transmit T. b brucei animal trypanosomosis and T. b. The success of colonizing a broad range of hosts, including humans, infers that trypanosomes acquired adaptation mechanisms allowing them to circumvent multiple immune killing mechanisms. These mechanisms have been best studied for T. brucei, with the cloned T. b.
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