Chronic <i><scp>T</scp>rypanosoma congolense</i> infections in mice cause a sustained disruption of the B‐cell homeostasis in the bone marrow and spleen

Obishakin, Emmanuel; Trez, Carl De; Magez, Stefan

doi:10.1111/pim.12099

Cited by 36 publications

(38 citation statements)

References 48 publications

(70 reference statements)

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“…Here Bam32, responsible for downstream signaling linked to BCR crosslinking, was shown to be crucial for prolonged parasitemia control, albeit redundant for early peak parasitemia elimination (80). This observation aligns with the finding that T. congolense infections cause a sustained disruption of the B cell homeostasis in bone marrow and spleen, and that the virulence index of different stocks in experimental mouse models correlates with the potential to drive B cell destruction (81). When it comes to immune destruction of the B cell compartment, this has also been documented in detail for T. vivax (82) and in more detail for T. brucei (83).…”

Section: Trypanosomes Avoid Antibody-mediated Killing By Destruction supporting

confidence: 78%

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

et al. 2020

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Salivarian trypanosomes are extracellular parasites that affect humans, livestock, and game animals around the world. Through co-evolution with the mammalian immune system, trypanosomes have developed defense mechanisms that allow them to thrive in blood, lymphoid vessels, and tissue environments such as the brain, the fat tissue, and testes. Trypanosomes have developed ways to circumvent antibody-mediated killing and block the activation of the lytic arm of the complement pathway. Hence, this makes the innate immune control of the infection a crucial part of the host-parasite interaction, determining infection susceptibility, and parasitemia control. Indeed, trypanosomes use a combination of several independent mechanisms to avoid clearance by the humoral immune system. First, perpetuated antigenic variation of the surface coat allows to escape antibody-mediated elimination. Secondly, when antibodies bind to the coat, they are efficiently transported toward the endocytosis pathway, where they are removed from the coat proteins. Finally, trypanosomes engage in the active destruction of the mammalian humoral immune response. This provides them with a rescue solution in case antigenic variation does not confer total immunological invisibility. Both antigenic variation and B cell destruction pose significant hurdles for the development of anti-trypanosome vaccine strategies. However, developing total immune escape capacity and unlimited growth capabilities within a mammalian host is not beneficial for any parasite, as it will result in the accelerated death of the host itself. Hence, trypanosomes have acquired a system of quorum sensing that results in density-dependent population growth arrest in order to prevent overpopulating the host. The same system could possibly sense the infection-associated host tissue damage resulting from inflammatory innate immune responses, in which case the quorum sensing serves to prevent excessive immunopathology and as such also promotes host survival. In order to put these concepts together, this review summarizes current knowledge on the interaction between Magez et al.Trypanosomosis and Innate Immune Control trypanosomes and the mammalian innate immune system, the mechanisms involved in population growth regulation, antigenic variation and the immuno-destructive effect of trypanosomes on the humoral immune system. Vaccine trials and a discussion on the role of innate immune modulation in these trials are discussed at the end.

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Section: Trypanosomes Avoid Antibody-mediated Killing By Destruction supporting

confidence: 78%

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

et al. 2020

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“…An underlying mechanism was revealed in recent studies using a T. brucei AnTat 1.1 mouse model of trypanosomiasis revealing that splenic transitional, marginal zone and follicular B cells are severely depleted from infected mice within 10 days after infection and remain depleted thereafter (Frenkel and Black, unpublished). Splenic B cells are also severely depleted in mice infected with T. congolense and T. vivax . Ongoing studies show that B‐cell depletion in the T. brucei AnTat 1.1 and C57BL/6 mouse model system also is accompanied by severe depletion of CD8 T cells and partial depletion of splenic CD4 T cells (Frenkel and Black, unpublished data).…”

Section: Why Vaccines Against Trypanosomiasis May Failmentioning

confidence: 88%

Prospects for vaccination against pathogenic African trypanosomes

Black

Mansfield

2016

Parasite Immunology

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“…Experiments were approved by the GUGC IACUC protocol n° LM16‐839/2018‐006. Parasitemia was assessed as previously described …”

Section: Methodsmentioning

confidence: 99%

Trypanosoma brucei brucei causes a rapid and persistent influx of neutrophils in the spleen of infected mice

Deleeuw

Phạm

Poorter

et al. 2019

Parasite Immunology

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Trypanosomosis is a chronic parasitic infection, affecting both humans and livestock. A common hallmark of experimental murine infections is the occurrence of inflammation and the associated remodelling of the spleen compartment. The latter involves the depletion of several lymphocyte populations, the induction of T‐cell‐mediated immune suppression, and the activation of monocyte/macrophage cell populations. Here, we show that in experimental T b brucei infections in mice, these changes are accompanied by the alteration of the spleen neutrophil compartment. Indeed, mature neutrophils are rapidly recruited to the spleen, and cell numbers remain elevated during the entire infection. Following the second peak of parasitemia, the neutrophil cell influx coincides with the rapid reduction of splenic marginal zone (MZ)B and follicular (Fo)B cells, as well as CD8+ T and NK1.1+ cells, the latter encompassing both natural killer (NK) and natural killer T (NKT) cells. This report is the first to show a comprehensive overview of all alterations in spleen cell populations, measured with short intervals throughout the entire course of an experimental T b brucei infection. These data provide new insights into the dynamic interlinked changes in spleen cell numbers associated with trypanosomosis‐associated immunopathology.

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Chronic Trypanosoma congolense infections in mice cause a sustained disruption of the B‐cell homeostasis in the bone marrow and spleen

Cited by 36 publications

References 48 publications

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

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

Prospects for vaccination against pathogenic African trypanosomes

Trypanosoma brucei brucei causes a rapid and persistent influx of neutrophils in the spleen of infected mice

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