Immunologic Responses to Vibrio cholerae in Patients Co-Infected with Intestinal Parasites in Bangladesh

Abstract
Infection with intestinal helminths is common and may contribute to the decreased efficacy of Vibrio cholerae vaccines in endemic compared to non-endemic areas. However, the immunomodulatory effects of concomitant intestinal parasitic infection in cholera patients have not been systematically evaluated. We evaluated V. cholerae-specific immune responses in a cohort of patients with severe cholera. 361 patients completed 21 days of observation and 53 (15%) had evidence of a concomitant intestinal parasitic infection based on direct microscopy. Although there were no significant differences in the vibriocidal or lipopolysaccharide (LPS)-specific immune responses to V. cholerae, helminth-infected cholera patients had decreased fecal and serum IgA immune responses to the B subunit of cholera toxin (CTB) as well as a more modest decrease in serum IgG response to CTB. These findings remained significant for all classes of helminth infection and when controlling for potential confounding variables such as age and nutritional status. Although we hypothesized the differential effect on CTB and LPS immune responses was due to T-cell-dependent immunomodulatory effects of helminth infection, we did not find additional evidence to support a classic Th1 or Th2 polarization of the immune response to V. cholerae infection related to parasite infection. The finding that helminth infection has a profound association with the mucosal humoral immune response to V. cholerae has implications for the development of protective immunity in cholera-endemic areas and provides an additional basis for deworming programs in cholera-endemic areas. Additional studies, including further characterization of the role of T cells in the immune response to human V. cholerae infection and the development of an animal model of co-infection, may provide additional insight into the mechanisms underlying these findings. Vibrio cholerae causes cholera, a severe diarrhea that may lead to fatal dehydration if not treated. Cholera occurs mostly in impoverished areas where there is poor sanitation and intestinal parasites are also common. However, little is known about the relationship between intestinal parasites and cholera. To learn about how parasites affect the immune response to Vibrio cholerae, this article describes 361 patients with cholera, including 53 who had intestinal parasitic infection. We found that cholera patients with parasitic worms had decreased antibody response to cholera toxin. The decrease was greatest in IgA antibodies, which are secreted in the intestine. However, patients with worm infection did not have a difference in their immune response to lipopolysaccharide, a sugar-based molecule that is important for immunity. These different effects on the immune response to cholera toxin and lipopolysaccharide could be explained by the effect of parasitic infection on CD4+ T cells, a type of cell that influences the development of the antibody response to proteins such as cholera toxin but may not always influence the response to sugar-based molecules. The finding that worm infection is associated with decreased immune responses to cholera provides an additional reason for deworming in cholera-endemic areas.

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