Salivarian Trypanosomosis: A Review of Parasites Involved, Their Global Distribution and Their Interaction With the Innate and Adaptive Mammalian Host Immune System

Abstract

Salivarian trypanosomes are single cell extracellular parasites that cause infections in a wide range of hosts. Most pathogenic infections worldwide are caused by one of four major species of trypanosomes including (i) Trypanosoma brucei and the human infective subspecies T. b. gambiense and T. b. rhodesiense, (ii) Trypanosoma evansi and T. equiperdum, (iii) Trypanosoma congolense and (iv) Trypanosoma vivax. Infections with these parasites are marked by excessive immune dysfunction and immunopathology, both related to prolonged inflammatory host immune responses. Here we review the classification and global distribution of these parasites, highlight the adaptation of human infective trypanosomes that allow them to survive innate defense molecules unique to man, gorilla, and baboon serum and refer to the discovery of sexual reproduction of trypanosomes in the tsetse vector. With respect to the immunology of mammalian host-parasite interactions, the review highlights recent findings with respect to the B cell destruction capacity of trypanosomes and the role of T cells in the governance of infection control. Understanding infection-associated dysfunction and regulation of both these immune compartments is crucial to explain the continued failures of anti-trypanosome vaccine developments as well as the lack of any field-applicable vaccine based anti-trypanosomosis intervention strategy. Finally, the link between infection-associated inflammation and trypanosomosis induced anemia is covered in the context of both livestock and human infections.

The Trypanosomal Transferrin Receptor of Trypanosoma Brucei—A Review

“…This is attributed to the fact that these latter parasites acquired the ability to resist trypanolytic molecular complexes, expressed by humans and higher primates as part of the innate immune system [20][21][22][23][24]. Due to this reason, and its implications for human medicine, the T. brucei clade has received greater attention and is better characterized, despite being it having a lower, though still potent, worldwide impact on veterinary economy, than for example T. congolense (Subgenus Nannomonas) or T vivax (Sub-genus Dutonella) [25]. By parasitizing the haemo-lymphatic environment, trypanosomes must reconcile two seemingly conflicting requirements, namely, to avoid the immune responses of the mammalian host by rapid variation of their plasma membrane as well as efficiently acquire potentially scarce nutritive resources from their environment via the same plasma membrane [29].…”

Hepatocyte-derived IL-10 plays a crucial role in attenuating pathogenicity during the chronic phase of T. congolense infection

“…It is however important to realize that B cell counts in the blood do not reveal whether B cell activation, the formation of plasma cells and antibody secretion, the induction of germinal center reactions, or the activation of CD4 + T follicular helper cell numbers and function, which are known to restrict T. congolense parasitemia [11,44], are impaired. However, this is highly likely since trypanosomes cause a general B cell depletion pathology, which is initiated by the very rapid disappearance of immature B cells in the bone marrow, as well as transitional and IgM + marginal zone B cells from the spleen, followed by a gradual depletion of Follicular B cells (FoB) [45,46]. Though the cause of B cell depletion is currently unknown, it was shown that the kinetics of this B cell loss and parasite outgrowth depends on different factors such as parasite virulence and the level of inflammation [45,46].…”

“…However, this is highly likely since trypanosomes cause a general B cell depletion pathology, which is initiated by the very rapid disappearance of immature B cells in the bone marrow, as well as transitional and IgM + marginal zone B cells from the spleen, followed by a gradual depletion of Follicular B cells (FoB) [45,46]. Though the cause of B cell depletion is currently unknown, it was shown that the kinetics of this B cell loss and parasite outgrowth depends on different factors such as parasite virulence and the level of inflammation [45,46]. Therefore, the observed reduced B cell numbers in TgAlbCre-IL10 -/mice at the later phase of infection is most likely due to a higher/persistent inflammatory immune response [45,47].…”

Infections With Extracellular Trypanosomes Require Control by Efficient Innate Immune Mechanisms and Can Result in the Destruction of the Mammalian Humoral Immune System

“…Over the years this parasite has occasionally caused havoc in Southern Europe due to illegal or ill-controlled import of infected livestock. The geographic distribution of all HAT and AT causing parasites and general aspects of the immunopathology related to their infections were recently reviewed by Radwanska et al (1).…”