Trypanosoma cruzi infection in mice induces a polyisotypic hypergammaglobulinaemia and parasite‐specific response involving high lgG2a concentrations and highly avid lgG1 antibodies

Abstract

SUMMARY Trypanosoma cruzi infection in BALB/c mice induced a reversible polyisotypic hypergammaglobulinaemia, with particularly high levels of IgG2a, IgM and IgE. Hypergammaglobulinaemia started during the acute phase of infection and persisted during chronic disease until 11–13 weeks post‐infection (w.p.i.), when immunoglobulin levels, with the exception of IgE, returned near normal values. Parasite‐specific antibodies counted for 14 to 23% of gammaglobulinaemia, in acute and chronic infection respectively. The titres of IgM antibodies rose from two w.p.i. IgA, IgE and IgG subclass antibodies built up gradually over the time of parasite clearance (i.e., between three and six w.p.i.). All antibody isotypes, including IgM reached significant and stable titres throughout chronic infection. IgG2a, IgG1 and IgM antibodies had constantly higher titres than the other antibody isotypes. The dominance of IgG2a antibodies was due to their high plasma concentrations, around 70% of all antibodies available in the chronic infection. IgG1 had the highest functional avidity, whereas its concentration corresponded to only 10% of the whole antibody fraction. These results indicate that T. cruzi infection in mice induces a polyisotypic humoral immune response, dominated by some antibody isotypes, with major differences in concentrations and functional avidities. This could be of crucial importance in determining the outcome of infection.

Why does GM1 induce a potent beneficial response to experimental Chagas disease?

“…itself corresponds to an intracellular time of three days, which is consistent with the practice of waiting five days to collect second generation parasites in vitro. N r is not far from the result we previously estimated ͑N r = 13.8͒ for the experiment of El Bouhdidi et al (1994) with BALB/c mice infected with the Tehuantepec strain of T. cruzi (Sibona et al, 2007) and it is consistent with the results ͑N r Ϸ 30͒ of a recent in vitro experiment using the CL strain (Coimbra et al, 2007). We remark that a higher in vitro value of N r is not surprising because of the better feeding of (and weaker constraints on) cells in a monolayer culture.…”

“…In fact, a Chagas patient is said to be cured of the infection only when specific antibodies are undetectable. The source term must depend on the parasite number because (i) a constant source cannot control the parasites and (ii) when the parasite numbers decrease, antibody generation must decrease, too (El Bouhdidi et al, 1994). We have chosen for this term the simplest form consistent with the available data.…”

“…When latency periods are larger than antibody lifetime, those parasites generate more persistent infections. (6) The values of the antibody parameters were obtained in Cossi Isasi et al (2001) from fits to the data of El Bouhdidi and co-workers (El Bouhdidi et al, 1994). Since these fits indicate that three antibody species (IgG1, IgG2a, and IgM) are needed to reproduce the parasite evolution data, we have used three antibody species in our simulations.…”

“…The learning times were obtained in Cossi Isasi et al (2001) from fits to the experimental results of El Bouhdidi et al (1994).…”

A Brucella Virulence Factor Targets Macrophages to Trigger B-cell Proliferation

“…This protein has hydroxyproline racemase activity (24), induces T-cell-independent B-cell proliferation, and is homologous to a B-lymphocyte mitogen of T. cruzi that is also involved in virulence (8,24,25). A hallmark of T. cruzi infection is the polyclonal B-cell proliferation observed during the acute phase that is accompanied by a strong hypergammaglobulinemia (26,27). Here we report that although PrpA induces B-cell proliferation, it does not bind to B-lymphocytes.…”