Helminth infections associated with multiple sclerosis induce regulatory B cells.
OBJECTIVE
To assess the importance of B-cell control during parasite infections in multiple sclerosis (MS) patients.


METHODS
Peripheral blood CD19+ B cells from 12 helminth-infected MS patients, 12 MS patients without infection, 10 patients infected with Trypanosoma cruzi, 8 subjects infected with Paracoccidioides brasiliensis, and 12 healthy control subjects were purified using magnetic cell sorting. Interleukin (IL)-4, IL-6, IL-10, tumor necrosis factor-alpha, lymphotoxin, transforming growth factor-beta, brain-derived neurotrophic factor, and nerve growth factor secretion were evaluated after stimulation with CDw32 L cells and CD40 antibody using enzyme-linked immunosorbent assays. The production of anti-myelin oligodendrocyte glycoprotein IgG and IgM antibodies was evaluated by enzyme-linked immunosorbent spot assays. Cell phenotype was assessed by flow cytometry.


RESULTS
Helminth infections in MS patients created a B-cell population producing high levels of IL-10, dampening harmful immune responses through a mechanism mediated, at least in part, by the ICOS-B7RP-1 pathway. The IL-10-producing B-cell phenotype detected expressed high levels of CD1d and was similar to the one observed in mature naive B2 cells (namely, CD11b(-), CD5(-), CD27(-), and IgD+). Moreover, B cells isolated from helminth-infected MS patients also produced greater amounts of brain-derived neurotrophic factor and nerve growth factor compared with those of normal subjects, T. cruzi-infected subjects, P. brasiliensis-infected subjects, or uninfected MS patients, raising the possibility that these cells may exert a neuroprotective effect on the central nervous system.


CONCLUSIONS
Increased production of B-cell-derived IL-10 and of neurotrophic factors are part of the parasite's regulation of host immunity and can alter the course of MS, potentially explaining environmental-related MS suppression observed in areas with low disease prevalence.
Correale
Jorge
J
Department of Neurology, Raúl Carrea Institute for Neurological Research (FLENI), Buenos Aires, Argentina. jcorreale@fleni.org.ar
Farez
Mauricio
M
Razzitte
Gabriela
G
D000328:Adult; D000818:Animals; D016175:B-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism* / Q000469:parasitology; D002454:Cell Differentiation / Q000276:immunology*; D005260:Female; D005500:Follow-Up Studies; D006373:Helminthiasis / Q000276:immunology* / Q000378:metabolism* / Q000469:parasitology; D006801:Humans; D016753:Interleukin-10 / Q000096:biosynthesis; D008297:Male; D009103:Multiple Sclerosis / Q000276:immunology* / Q000469:parasitology; D009414:Nerve Growth Factors / Q000096:biosynthesis; D010228:Paracoccidioides / Q000276:immunology; D014349:Trypanosoma cruzi / Q000276:immunology / Q000469:parasitology
D009414:Nerve Growth Factors; D016753:Interleukin-10