Quantitative Differences in Immune Responses in Mouse Strains that Differ in their Susceptibility to Trypanosoma brucei brucei Infection

Namangala, Boniface; Baetseĺier, Patrick De; Beck, Alain

doi:10.1292/jvms.71.951

Cited by 7 publications

(9 citation statements)

References 20 publications

(37 reference statements)

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“…Another possible explanation could be the formation of immune complex of specific antibodies with the parasite antigens making this unable to measure IgGs solely in circulation [51][52]. Reduction of antigen-stimulated cytokine levels observed after 8 dpi is not conducive to parasite control, since IFN-γ is associated with resistance to African trypanosomes [53][54][55] and TNF-α was shown to be essential to controlling T. vivax infection in mice [56]. These changes in both the IgG1/IgG2a ratio and the cytokine profiles after challenge indicate a transition from a Th1-type to Th2-type response, which is a typical feature of uncontrolled infections in trypanosomatids [57][58][59][60][61] and is observed in naturally-infected cattle [62].…”

Section: Discussionmentioning

confidence: 99%

Vivaxingenes encode highly immunogenic non-variant antigens unique to theTrypanosoma vivaxcell-surface

Romero-Ramirez

Casas-Sánchez

Autheman

et al. 2022

Preprint

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Trypanosoma vivax is a unicellular hemoparasite, and a principal cause of animal African trypanosomiasis (AAT), a vector-borne and potentially fatal disease of livestock across sub-Saharan Africa. Previously, we identified diverse T. vivax-specific genes that were predicted to encode cell surface proteins. Here, we examine the immune responses of naturally and experimentally infected hosts to many of these unique parasite antigens, to identify immunogens that could become vaccine candidates. Immunoprofiling of host serum showed that one particular family (Fam34) elicits a consistent IgG antibody response. This gene family, which we now call Vivaxin, encodes at least 124 transmembrane glycoproteins that display quite distinct expression profiles and patterns of genetic variation. We focused on one gene (viv-β8) that is among the most immunogenic and highly expressed but displays minimal polymorphism. VIVβ8 was localized across the cell body and flagellar membrane, suggesting that vivaxin is substantial family of novel surface proteins. Although vaccination of mice with VIVβ8 adjuvanted with Quil-A elicits a strong, balanced immune response and delays parasite proliferation in some animals, ultimately, it does not prevent disease. However, our phylogenetic analysis shows vivaxin includes other antigens shown to induce immunity against T. vivax. Thus, the introduction of vivaxin represents an important advance in our understanding of the T. vivax cell surface. Besides being a source of proven and promising vaccine antigens, the gene family is clearly an important component of the parasite glycocalyx, with potential to influence the host-parasite interaction.

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Section: Discussionmentioning

confidence: 99%

Vivaxingenes encode highly immunogenic non-variant antigens unique to theTrypanosoma vivaxcell-surface

Romero-Ramirez

Casas-Sánchez

Autheman

et al. 2022

Preprint

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“…It is intriguing to note that the same pro‐inflammatory mediators inducing immunosuppression, depending on their concentrations in body fluids, are reportedly critical in parasite control in the mammalian host and may be linked with increased survival of the trypanosome‐infected host. For instance, T‐cell‐derived IFN‐γ is documented to be crucial for survival of animals infected with either T. b. brucei or T. congolense parasites (83–88). Furthermore, TNF‐α has been reported to be crucial in the control of various T. congolense strains including T. congolense TC13, STIB68, IL1180, J4/23, TRT55 and TRT17 clones, as evidenced by hypersusceptibility of infected TNF‐deficient mice, with a more dramatic effect in T. congolense TC13 strain whose median survival reduced from 133 days in wild‐type mice to 18 days in TNF‐deficient animals (89).…”

Section: Trypanosome‐induced Suppression Of Lymphocyte Proliferative mentioning

confidence: 99%

“…There is a large body of evidence suggesting that in most trypanosome infection models, a strong Th1 response is protective, mainly during the early trypanosomosis (22,83–88). Trypanosomes may evade such immune responses by inducing irrelevant immune responses during the early stage of infection such as enhancement of (i) the production of Th2 cytokines and (ii) regulatory T‐cell activation that results in increased production of IL‐10 and TGF‐β, both of which suppress early protective Th1 responses and hence favour parasite survival (18,89,91).…”

Section: Trypanosome‐induced T‐cell Defectsmentioning

confidence: 99%

“…Because of their critical role in secreting anti‐trypanosome Abs (16,83,84,86,89), B cells are obvious targets for African trypanosomes. Both murine and bovine trypanosomosis are characterized by polyclonal B cell (CD5 + B cell) activation as evidenced by increased number of B cells and significant elevations in plasma Abs (17,24,92).…”

Section: Trypanosome‐induced B Cell Defectsmentioning

confidence: 99%

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How the African trypanosomes evade host immune killing

Namangala

2011

Parasite Immunology

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Unlike other protozoan parasites, African trypanosomes never enter the host cell at any stage of their development. Instead, these parasites swim freely in the immunologically hostile host tissue fluids. During the course of infection, a complex interaction between the host immune responses and trypanosome survival strategies occurs. Continued contacts with the host's immune system occurring during the course of infection could have provided strong selection pressure for African trypanosomes to evolve very sophisticated mechanisms to evade immune killing to survive the hostile immunological environment in the infected host. This review discusses some of the documented immunological evasion mechanisms African trypanosomes employ for their survival and perpetuity.

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“…Depending on the trypanosome species and the stage of infection, different cellular sources could contribute to IL-10 production such as NK cells, CD8 + T cells and CD4 + T cells around peak parasitaemia as well as B cells and plasma cells, myeloid cells and hepatocytes as the infection progresses ( 45 , 48 – 51 ). Furthermore, the level of IL-10 induction might also differ between different mouse strains ( 52 ).…”

Section: Introductionmentioning

confidence: 99%

The Role of MIF and IL-10 as Molecular Yin-Yang in the Modulation of the Host Immune Microenvironment During Infections: African Trypanosome Infections as a Paradigm

et al. 2022

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African trypanosomes are extracellular flagellated unicellular protozoan parasites transmitted by tsetse flies and causing Sleeping Sickness disease in humans and Nagana disease in cattle and other livestock. These diseases are usually characterized by the development of a fatal chronic inflammatory disease if left untreated. During African trypanosome infection and many other infectious diseases, the immune response is mediating a see-saw balance between effective/protective immunity and excessive infection-induced inflammation that can cause collateral tissue damage. African trypanosomes are known to trigger a strong type I pro-inflammatory response, which contributes to peak parasitaemia control, but this can culminate into the development of immunopathologies, such as anaemia and liver injury, if not tightly controlled. In this context, the macrophage migration inhibitory factor (MIF) and the interleukin-10 (IL-10) cytokines may operate as a molecular “Yin-Yang” in the modulation of the host immune microenvironment during African trypanosome infection, and possibly other infectious diseases. MIF is a pleiotropic pro-inflammatory cytokine and critical upstream mediator of immune and inflammatory responses, associated with exaggerated inflammation and immunopathology. For example, it plays a crucial role in the pro-inflammatory response against African trypanosomes and other pathogens, thereby promoting the development of immunopathologies. On the other hand, IL-10 is an anti-inflammatory cytokine, acting as a master regulator of inflammation during both African trypanosomiasis and other diseases. IL-10 is crucial to counteract the strong MIF-induced pro-inflammatory response, leading to pathology control. Hence, novel strategies capable of blocking MIF and/or promoting IL-10 receptor signaling pathways, could potentially be used as therapy to counteract immunopathology development during African trypanosome infection, as well as during other infectious conditions. Together, this review aims at summarizing the current knowledge on the opposite immunopathological molecular “Yin-Yang” switch roles of MIF and IL-10 in the modulation of the host immune microenvironment during infection, and more particularly during African trypanosomiasis as a paradigm.

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Quantitative Differences in Immune Responses in Mouse Strains that Differ in their Susceptibility to Trypanosoma brucei brucei Infection

Cited by 7 publications

References 20 publications

Vivaxingenes encode highly immunogenic non-variant antigens unique to theTrypanosoma vivaxcell-surface

Vivaxingenes encode highly immunogenic non-variant antigens unique to theTrypanosoma vivaxcell-surface

How the African trypanosomes evade host immune killing

The Role of MIF and IL-10 as Molecular Yin-Yang in the Modulation of the Host Immune Microenvironment During Infections: African Trypanosome Infections as a Paradigm

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