Abstract

Vibrio cholerae, the cause of cholera, induces both innate and adaptive immune responses in infected humans. Leptin is a hormone that plays a role in both metabolism and mediating immune responses. We characterized leptin levels in 11 children with cholera in Bangladesh, assessing leptin levels on days 2, 7, 30, and 180 following cholera. We found that patients at the acute stage of cholera had significantly lower plasma leptin levels than matched controls, and compared with levels in late convalescence. We then assessed immune responses to V. cholerae antigens in 74 children with cholera, correlating these responses to plasma leptin levels on day 2 of illness. In multivariate analysis, we found an association between day 2 leptin levels and development of later anti-cholera toxin B subunit (CtxB) responses. This finding appeared to be limited to children with better nutritional status. Interestingly, we found no association between leptin levels and antibody responses to V. cholerae lipopolysaccharide, a T cell–independent antigen. Our results suggest that leptin levels may be associated with cholera, including the development of immune responses to T cell–dependent antigens.

Highlights

  • Vibrio cholerae is a Gram negative organism and the cause of cholera, a severe dehydrating illness of humans.[1]

  • When we stratified children by nutritional status, we found that day 2 plasma leptin levels correlated with subsequent development of IgG antibody responses to cholera toxin B subunit (CtxB) on day 30 only among children who were not moderately or severely undernourished by WAZ and WHZ (Figure 2)

  • We found that leptin levels are low during the acute stage of cholera compared with levels in healthy matched controls and that plasma leptin levels rise following cholera during late convalescence

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Summary

Introduction

Vibrio cholerae is a Gram negative organism and the cause of cholera, a severe dehydrating illness of humans.[1]. Many of the individuals who are at risk for cholera are afflicted by other health conditions, including nutritional deficiencies. Leptin is a hormone that is involved in both metabolism and mediating immune responses during human infection.[3] Leptin is primarily released into the plasma by adipose tissue, but is produced by gastric and colonic epithelial cells and T cells during acute inflammation.[4] Undernourished individuals have lower leptin levels in the circulation than wellnourished individuals.[5] In general, males have lower leptin levels than females, perhaps reflecting differences in the amount and distribution of adipose tissue.[6] The receptor for the leptin molecule is expressed on a number of different cell types, including intestinal epithelial and immune cells, such as macrophages, T cells, natural killer cells, and polymorphonuclear leukocytes, as well as other cell types such as neurons.[7] Alterations in the leptin receptor and leptin gene expression have been associated with changes in immune responses and increased susceptibility to infection.[8] Since cholera often occurs in populations with undernourishment or other nutritional deficiencies, we were interested in characterizing plasma leptin levels in children with cholera who were 5 years of age or younger in Dhaka, Bangladesh, and the association of these levels with subsequent immune responses. We hypothesized that leptin levels would increase in response to cholera infections, acting as an acute inflammatory cytokine

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