Macrophages as primary target cells and mediators of immune dysfunction in African trypanosomiasis

Cattle were vaccinated with Brucella abortus (S19) vaccine during acute (25 days) and chronic (25 weeks) Trypanosoma congolense and chronic Trypanosoma vivax (25 weeks) infections in order to determine the effect of such infections on the antibody response to the vaccine. It was found that the specific antibody responses of IgG1 and IgG2 sub-classes were profoundly depressed (80%) in both the acute and chronic infections with T. congolense. Whereas IgM antibody response was also profoundly depressed (90%) in cattle with the acute infection, it was only 50% depressed in those with chronic infection. There was no depression of IgG1, IgG2, or IgM in cattle infected with T. vivax. These animals, however, had no detectable parasitaemia at the time of vaccination and thereafter. These results suggest that during acute infection with T. congolense depressive mechanisms could be acting on the afferent arm of the immune response, namely, antigen recognition and/or processing.

Section: Discussionsupporting

confidence: 65%

Immune depression in bovine trypanosomiasis: effects of acute and chronic Trypanosoma congolense and chronic Trypanosoma vivax infections on antibody response to Brucella abortus vaccine

Rurangirwa

Musoke

Nantulya

et al. 1983

“…To date, despite the pivotal role played by macrophages in T cell hyporesponsiveness in African trypanosomeinfected animals, little attention has been paid to the possible alterations of their antigen presentation capacity. An increase in macrophage phagocytic activity during infection with Trypanosoma b. brucei has been described in mice (Stevens & Moulton 1978, Grosskinsky & Askonas 1981 and livestock (MacKenzie et al 1978, Kissling et al 1982. Infection with T. b. brucei is also associated with up-regulation of MHC class II molecules expression on macrophages, and increased secretion of IL-1, prostaglandins, nitric oxide (NO) and tumour necrosis factor (TNF)-a by macrophages (Grosskinsky & Askonas 1981, Sileghem et al 1989b, Schleifer & Mans®eld 1993, Darji et al 1996, Beschin et al 1998.…”

Section: Introductionmentioning

confidence: 99%

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

Namangala

Brys

Magez

et al. 2000

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.

“…This form of suppression is observed in hypersusceptible C3H/He mice and inhibits antibody secretion from parasite-induced and other antibody-containing cells. At this point we do not know if this form of immunosuppression occurs in mice other than those of the C3H/He strain nor do we know if it is macrophage or T-cell dependent as has been shown for other forms of Trypanosome-induced immunosuppression (Corsini et al 1977, Jayawardena, Waksman & Eardley 1978, Wellhausen & Mansfield 1979, Grosskinsky & Askonas 1981. The defect in antibody secretion in T. b. brucei-infected C3H/He mice was dependent on the presence of living parasites or, more likely, on short-lived factors from degenerating parasites but could not be induced, during the first 4 days after RRBC challenge of normal C3H/He mice, by injection of large numbers of living parasites.…”

Section: Discussionmentioning

confidence: 98%

Regulation of parasite‐specific antibody responses in resistant (C57BL/6) and susceptible (C3H/HE) mice infected with Trypanosoma (trypanozoon) brucei brucei

Black

Sendashonga

Webster

et al. 1986

After infection with 10(3) T. brucei GUTat 3.1, C57BL/6 mice produced antibody responses and controlled the first parasitaemic wave whereas C3H/He mice did not. The inability of C3H/He mice to control parasitaemia resulted from an impaired ability of parasite-induced antibody-containing cells to secrete immunoglobulin. Antibody-containing cells in infected C3H/He mice regained the ability to secrete antibody within 24 h after trypanosome elimination by treatment with Berenil, suggesting that the block in antibody secretion was maintained by living parasites or short-lived components of degenerating parasites. Infected C3H/He mice also had an impaired ability to produce a rabbit erythrocyte-specific antibody response on challenge with rabbit erythrocytes and this response recovered when parasites were eliminated from the blood 24 h before analysis. It was not possible to inhibit secretion of antibody by rabbit erythrocyte-induced plasma cells either by incubating them with serum from infected C3H/He mice or by injecting large numbers of living trypanosomes into C3H/He mice already responding to rabbit erythrocytes. The process leading to failure of parasite and rabbit erythrocyte-induced antibody-containing cells to become high rate antibody-secreting cells was not identified but did not appear to correlate with any obvious change in the intra-cellular morphology of the antibody-containing cells.