Trypanosoma brucei brucei infection impairs MHC class II antigen presentation capacity of macrophages

Abstract

During African trypanosomiasis, macrophages play a central role in T cell hyporesponsiveness to parasite-related and unrelated antigens. In this study, the ability of macrophages from Trypanosoma b. brucei-infected mice to present exogenous antigens to a major histocompatibility complex (MHC) class II-restricted CD4+ T cell hybridoma was analysed. We demonstrate that the antigen presentation capacity of macrophages from infected mice is markedly reduced as a result of a lower expression of [MHC class II-peptide] complexes on their plasma membrane. This defect did not result from a decreased antigen uptake/catabolism, a reduced MHC class II and intercellular adhesion molecule 1 expression on the surface of macrophages, a decreased affinity of MHC class II molecules for antigenic peptides, a competition between exogenous and parasite antigens, or the generation of inhibitory peptides. Our data indicate that the step resulting in coexpression of processed antigens and MHC class II molecules is affected in T. b. brucei-infected mice. Additionally, macrophages from infected mice secreted IL-10 that in turn contributes to the impairment of T cell activation.

Tsetse Fly Saliva Accelerates the Onset ofTrypanosoma bruceiInfection in a Mouse Model Associated with a Reduced Host Inflammatory Response

“…In order to maintain controlled growth, trypanosomes coordinately alter their major surface antigen (VSG) coat and modify functions of antigen-presenting cells (8,43) as well as T lymphocytes (56) and B lymphocytes (2). During a trypanosome infection, an equilibrated balance between inflammation and anti-inflammation was shown to be crucial for successfully controlling parasites while limiting the outcome of immune pathology (33,44).…”

“…In order to escape the adaptive immune system, trypanosomes undergo antigenic variation by altering their major surface antigen, the variantspecific surface glycoprotein (VSG) (6). Beside this immune evasion mechanism, trypanosomes have been shown to modulate immune functions of macrophages (8,43), T lymphocytes (56), and B lymphocytes (2). The main host immune effectors involved in parasite control are considered to be trypanosomespecific antibodies (30) and the cytokine tumor necrosis factor (TNF) (33).…”

Modulation of innate immunity by African Trypanosomes

“…To date, several studies have demonstrated that APC functions are significantly altered during experimental trypanosomiasis (Paulnock et al 1989;Namangala et al 2000;Dagenais et al 2009b).…”

Increased Activation and Oligoclonality of Peripheral CD8+T Cells in the Chronic Human Helminth Infection Alveolar Echinococcosis

“…This was demonstrated for parasitic diseases onchocerciasis and filiariasis (6,18,26,32) as well as in a group of Alaskan patients severely infected with E. multilocularis. The Alaskan patients were shown to have a depressed proliferation rate by using vesicular fluid antigen (16).…”