Detrimental Effect ofTrypanosoma brucei bruceiInfection on Memory B Cells and Host Ability to Recall Protective B-cell Responses

Abstract

Background Trypanosoma brucei brucei (T. b. brucei) evades host immune responses by multiple means, including the disruption of B cell homeostasis. This hampers anti-trypanosome vaccine development. As the cellular mechanism underlying this pathology has never been addressed, our study focuses on the fate of memory B cells (MBCs) in vaccinated mice upon trypanosome challenge. Methods A trypanosome variant surface glycoprotein (VSG) and fluorescent phycoerythrin (PE) were used as immunization antigens. Functional and cellular characteristics of antigen-specific MBCs were studied after homologous and heterologous parasite challenge. Results Immunization with AnTat 1.1 VSG triggers a specific antibody response and isotype-switched CD73 +CD273 +CD80 + MBCs, delivering 90% sterile protection against a homologous parasite challenge. As expected, AnTat 1.1 VSG immunization does not protect against infection with heterologous VSG-switched parasites. After successful curative drug treatment, mice were shown to have completely lost their previously induced protective immunity against the homologous parasites, coinciding with the loss of vaccine-induced MBCs. A PE immunization approach confirmed that trypanosome infections cause the general loss of antigen-specific splenic and bone marrow MBCs, and a reduction in antigen-specific IgGs. Conclusion Trypanosomosis induces general immunological memory loss. This benefits the parasites by reducing the stringency for antigenic variation requirements.

Tipping the balance between erythroid cell differentiation and induction of anemia in response to the inflammatory pathology associated with chronic trypanosome infections

“…Separated parasites were then collected in phosphate saline glucose buffer (44 mM NaCl, 57 mM Na 2 HPO 4 , 3 mM NaH 2 PO 4 , 55 mM glucose) before being washed twice with DPBS (Invitrogen, Carlsbad, CA) by centrifuging at 1500 x G for 7 minutes, followed by 30 minutes incubation on ice in 1mL Baltz buffer (0.125 M phosphate buffer pH 5.5 containing 1% Glucose) and 5 minutes incubation at 37°C. Soluble VSG (sVSG) present in the supernatant was collected after 10 minutes centrifugation of the sample at 15000 x g. The concentration of sVSG was then estimated using the Bradford protein assay kit (Bio-rad, CA, USA), before being frozen at -20°C (41).…”

From helping to regulating – A transcriptomic profile of Ifng+ Il10+ Il21+ Cd4+ Th1 cells indicates their role in regulating inflammation during experimental trypanosomosis

“…Antigenic variation of their surface coat and inhibition of complement-mediated lysis are the main tools employed by trypanosomes to ensure successful development of infection (14,15). In addition, trypanosomes have acquired the capacity to manipulate the host antibody production capacity by directly affecting B cells and plasma cells (PCs) (16)(17)(18)(19). Here, the recent implementation scRNA-seq analysis has provided a detailed cellular map outlining how infection-associated disruption of B cell homeostasis takes place, and how accelerated terminal differentiation into PCs in the absence of naïve B cell replenishment results in the overall abrogation of the host antibody production during chronic trypanosome infections (10,20).…”

Pathogenicity and virulence of African trypanosomes: From laboratory models to clinically relevant hosts

“…Given the key role of antigen-specific antibodies, a notable parasite-driven phenotype is the destruction of host immune memory, with trypanosome infection of mice resulting in ablation of B cell memory via killing of B cells. This included the loss of memory to previously exposed non-trypanosome antigens [ 115 ]; this was recently shown to specifically involve the loss of memory B cells from infected animals [ 116 ]. This effect has also been shown to occur in mouse infections with T. congolense [ 117 ], and observed disruptions to splenic architecture including lymphocyte-depleted germinal centers and depletion of splenic B cells in mice infected with T. vivax are consistent with the phenotype also occurring in infections with this species [ 118 , 119 ].…”