Suppressive macrophages occurring in murine Trypanosoma brucei infection inhibit T‐cell responses in vivo and in vitro

Abstract

Intraperitoneal injection of Trypanosoma brucei AnTat 1.1 into mice of the C3H.He, BALB/c or C57BL/6 strains resulted in impaired immune responses from day 3 onwards, as measured by the reduction in DNA synthesis in spleen cell populations stimulated with concanavalin A (Con-A) in vitro. Adherent cells from the peritoneum (PC) or from the spleen of infected mice, consisting predominantly of macrophages, caused a 60-80% reduction of the Con-A response in spleen cells from syngeneic recipients 3-4 days after transfer in vivo. Adherent PC from irradiated or athymic mice were equally suppressive. Spleen cells from infected mice reduced the proliferative response of spleen cells from uninfected mice upon co-cultivation in vitro. This dominant suppressive effect was abolished after the selective removal of macrophages from the spleen cell population by treatment with L-leucine methylester. Moreover, the macrophage-depleted spleen cells from infected mice responded normally to Con-A provided they were supplemented with splenic adherent cells from naive mice as a source of accessory cells. Both the cell transfer and co-cultivation experiments suggest that infection with African trypanosomes changes the properties of macrophages to a state which allows them actively to suppress immune responses.

Trypanosoma brucei infection elicits nitric oxide-dependent and nitric oxide-independent suppressive mechanisms

“…Trypanosome-elicited immunosuppression was amply documented in humans [2], cattle [3], and laboratory rodents [4]. Although many mechanisms have been proposed to account for the induction of this immunosuppressive state there is accumulating evidence that suppressive macrophages, elicited during trypanosome infections [5], are the central effector cells in the inhibition of lymphoproliferative responses to mitogens and antigens [6][7][8].…”

Low-Dose Intradermal Infection with Trypanosoma congolense Leads to Expansion of Regulatory T Cells and Enhanced Susceptibility to Reinfection

“…Trypanosome-infected animals (including humans, cattle, and mice) show marked suppression of the immune response to vaccines as well as to T-cell mitogens, including concanavalin A (ConA) and phytohemagglutinin (PHA) (34)(35)(36)(37)(38)(39)(40)(41)(42)(43). In addition, infected mice also show a reduced antibody response to sheep red blood cells (SRBC) following immunization (44)(45)(46)(47)(48).…”

Splenic Denervation Suppresses mRNA Gene Expression and Protein Production of IL-1β and IL-6 by Peritoneal Macrophages in both <i>Trypanosoma brucei brucei</i>-Infected and Non-Infected Rats

“…Animals infected with African trypanosomes exhibit profound changes in their immune systems, one of which is generalized immunosuppression that affects both cellular and humoral immune responses [17]. Immunosuppression is a common feature of many infections.…”