Antibody‐mediated control of <i><scp>T</scp>rypanosoma vivax</i> infection fails in the absence of tumour necrosis factor

Greca, Florencia La; Haynes, Carole; Stijlemans, Benoı̂t; Trez, Carl De; Magez, Stefan

doi:10.1111/pim.12106

Cited by 20 publications

(24 citation statements)

References 24 publications

(34 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Finally, in case of T. vivax, infections were done in µMT mice as well as a number of cytokine deficient mice, but not in IgM deficient mice. Results available so far show that the combination of anti-trypanosome antibodies and an inflammatory immune environment, in particular the presence of TNF, is needed for proper parasitemia control, very similarly to the results described for T. congolense (65).…”

Section: Trypanosomes Avoid Antibody-mediated Killing By Dynamic Surfsupporting

confidence: 69%

“…Similarly, these C5deficient mice were capable of controlling T. musculi infections (93), as well as T. congolense infections (94). Also AKR mice were used to study the progression of infection in models for both T. b. rhodesiense (95) and T. vivax (65), showing again that peak parasitemia control as well as peak parasitemia clearance occurs in the absence of C5, and by consequence in the absence of complement-mediated trypanolysis. The lack of C5 involvement in trypanosomosis control is further corroborated by the fact that T. congolense infections hardly affected plasma C5 levels in a range of different mouse models, including highly susceptible and highly tolerant strains (96).…”

Section: Serum Complement Factors Mediate Parasitemia Control In Vivomentioning

confidence: 99%

See 1 more Smart Citation

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

View full text Add to dashboard Cite

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.

show abstract

Section: Trypanosomes Avoid Antibody-mediated Killing By Dynamic Surfsupporting

confidence: 69%

Section: Serum Complement Factors Mediate Parasitemia Control In Vivomentioning

confidence: 99%

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

View full text Add to dashboard Cite

show abstract

“…This review will focus on two most relevant AAT species T. brucei and T. congolense , given that for both parasites, established murine models and field studies in the economically and clinically relevant host (cattle) are available (45). While for T. vivax , field study information is scanty, hardly any representative experimental data are available as these parasites do not grow in mice unless they are carefully adapted (23, 46, 47). However, there is prospect since Minoprio and coworkers were able to establish a murine model for T. vivax (48).…”

Section: Introductionmentioning

confidence: 99%

African Trypanosomes Undermine Humoral Responses and Vaccine Development: Link with Inflammatory Responses?

et al. 2017

View full text Add to dashboard Cite

African trypanosomosis is a debilitating disease of great medical and socioeconomical importance. It is caused by strictly extracellular protozoan parasites capable of infecting all vertebrate classes including human, livestock, and game animals. To survive within their mammalian host, trypanosomes have evolved efficient immune escape mechanisms and manipulate the entire host immune response, including the humoral response. This report provides an overview of how trypanosomes initially trigger and subsequently undermine the development of an effective host antibody response. Indeed, results available to date obtained in both natural and experimental infection models show that trypanosomes impair homeostatic B-cell lymphopoiesis, B-cell maturation and survival and B-cell memory development. Data on B-cell dysfunctioning in correlation with parasite virulence and trypanosome-mediated inflammation will be discussed, as well as the impact of trypanosomosis on heterologous vaccine efficacy and diagnosis. Therefore, new strategies aiming at enhancing vaccination efficacy could benefit from a combination of (i) early parasite diagnosis, (ii) anti-trypanosome (drugs) treatment, and (iii) anti-inflammatory treatment that collectively might allow B-cell recovery and improve vaccination.

show abstract

“…B cells are essential for post‐peak parasite removal and prolonged survival . Mouse models of African trypanosomosis show that several trypanosome species cause a sustained loss in splenic and bone marrow B‐cell populations . Vaccination experiments indicate that trypanosome infection leads to abolishment of previously induced memory responses to African trypanosomes and even to unrelated pathogens .…”

Section: Introductionmentioning

confidence: 99%

IFN‐γ mediates early B‐cell loss in experimental African trypanosomosis

Cnops

Trez

Bulté

et al. 2015

Parasite Immunology

Self Cite

View full text Add to dashboard Cite

SUMMARYAfrican trypanosomes infect humans and animals throughout the African continent. These parasites maintain chronic infections by various immune evasion strategies. While antigenic variation of their surface coat is the most studied strategy linked to evading the host humoral response, African trypanosomes also induce impaired B-cell lymphopoiesis, the destruction of the splenic B-cell compartment and abrogation of protective memory responses. Here we investigate the mechanism of follicular B-cell destruction. We show that during infection follicular B cells undergo apoptosis, correlating to enhanced Fas death receptor surface expression. Investigation of various type 1 cytokine knockout mice indicates a crucial role of IFN-c in the early onset of FoB cell destruction. Indeed, both IFN-c À/À and IFN-cR À/À mice are protected from trypanosomosis-associated FoB cell depletion, exhibiting an inhibition of B-cell apoptosis as well as a reduced activation of FoB cells during the first week post-infection. The data presented herein offer new insights into B-cell dysfunctioning during experimental African trypanosome infections.

show abstract

Antibody‐mediated control of Trypanosoma vivax infection fails in the absence of tumour necrosis factor

Cited by 20 publications

References 24 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

African Trypanosomes Undermine Humoral Responses and Vaccine Development: Link with Inflammatory Responses?

IFN‐γ mediates early B‐cell loss in experimental African trypanosomosis

Contact Info

Product

Resources

About