Volume 93, Issue 2
  • ISSN: 0002-9637
  • E-ISSN: 1476-1645



, 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 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 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.

[open-access] This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


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  1. Harris JB, LaRocque RC, Qadri F, Ryan ET, Calderwood SB, , 2012. Cholera. Lancet 379: 24662476.[Crossref] [Google Scholar]
  2. WHO, 2010. WHO position paper on cholera vaccines. Wkly Epidemiol Rec 85: 117128. [Google Scholar]
  3. Procaccini C, Pucino V, De Rosa V, Marone G, Matarese G, , 2014. Neuro-endocrine networks controlling immune system in health and disease. Front Immunol 5: 143.[Crossref] [Google Scholar]
  4. Sobhani I, Bado A, Vissuzaine C, Buyse M, Kermorgant S, Laigneau J-P, Attoub S, Lehy T, Henin D, Mignon M, Lewin MJ, , 2000. Leptin secretion and leptin receptor in the human stomach. Gut 47: 178183.[Crossref] [Google Scholar]
  5. Faggioni R, Feingold KR, Grunfeld C, , 2001. Leptin regulation of the immune response and the immunodeficiency of malnutrition. FASEB J 15: 25652571.[Crossref] [Google Scholar]
  6. Garcia-Mayor RV, Andrade MA, Rios M, Lage M, Dieguez C, Casanueva FF, , 1997. Serum leptin levels in normal children: relationship to age, gender, body mass index, pituitary-gonadal hormones, and pubertal stage. J Clin Endocrinol Metab 82: 28492855. [Google Scholar]
  7. Mackey-Lawrence NM, Petri WA, , 2012. Leptin and mucosal immunity. Mucosal Immunol 5: 18.[Crossref] [Google Scholar]
  8. Duggal P, Guo X, Haque R, Peterson KM, Ricklefs S, Mondal D, Alam F, Noor Z, Verkerke HP, Marie C, Leduc CA, Chua SC, Myers MG, Leibel RL, Houpt E, Gilchrist CA, Sher A, Porcella SF, Petri WA, , 2011. A mutation in the leptin receptor is associated with Entamoeba histolytica infection in children. J Clin Invest 121: 11911198.[Crossref] [Google Scholar]
  9. Weil AA, Chowdhury F, Khan AI, Leung DT, Uddin T, Begum YA, Saha NC, Charles RC, LaRocque RC, Harris JB, Ryan ET, Qadri F, Calderwood SB, , 2012. Frequency of reexposure to Vibrio cholerae O1 evaluated by subsequent vibriocidal titer rise after an episode of severe cholera in a highly endemic area in Bangladesh. Am J Trop Med Hyg 87: 921926.[Crossref] [Google Scholar]
  10. Qadri F, Wenneras C, Albert MJ, Hossain J, Mannoor K, Begum YA, Mohi G, Salam MA, Sack RB, Svennerholm AM, , 1997. Comparison of immune responses in patients infected with Vibrio cholerae O139 and O1. Infect Immun 65: 35713576. [Google Scholar]
  11. Qadri F, Ahmed F, Karim MM, Wenneras C, Begum YA, Salam MA, Albert MJ, McGhee JR, , 1999. Lipopolysaccharide- and cholera toxin-specific subclass distribution of B-cell responses in cholera. Clin Diagn Lab Immunol 6: 812818. [Google Scholar]
  12. Rahman A, Rashu R, Bhuiyan TR, Chowdhury F, Khan AI, Islam K, LaRocque RC, Ryan ET, Wrammert J, Calderwood SB, Qadri F, Harris JB, , 2013. Antibody-secreting cell responses after Vibrio cholerae O1 infection and oral cholera vaccination in adults in Bangladesh. Clin Vaccine Immunol 20: 15921598.[Crossref] [Google Scholar]
  13. Wieland CW, Florquin S, Chan ED, Leemans JC, Weijer S, Verbon A, Fantuzzi G, van der Poll T, , 2005. Pulmonary Mycobacterium tuberculosis infection in leptin-deficient ob/ob mice. Int Immunol 17: 13991408.[Crossref] [Google Scholar]
  14. Uddin T, Harris JB, Bhuiyan TR, Shirin T, Uddin MI, Khan AI, Chowdhury F, LaRocque RC, Alam NH, Ryan ET, Calderwood SB, Qadri F, , 2011. Mucosal immunologic responses in cholera patients in Bangladesh. Clin Vaccine Immunol 18: 506512.[Crossref] [Google Scholar]
  15. Arifuzzaman M, Rashu R, Leung DT, Hosen MI, Bhuiyan TR, Bhuiyan MS, Rahman MA, Khanam F, Saha A, Charles RC, LaRocque RC, Weil AA, Clements JD, Holmes RK, Calderwood SB, Harris JB, Ryan ET, Qadri F, , 2012. Antigen-specific memory T cell responses after vaccination with an oral killed cholera vaccine in Bangladeshi children and comparison to responses in patients with naturally acquired cholera. Clin Vaccine Immunol 19: 13041311.[Crossref] [Google Scholar]
  16. Palacio A, Lopez M, Perez-Bravo F, Monkeberg F, Schlesinger L, , 2002. Leptin levels are associated with immune response in malnourished infants. J Clin Endocrinol Metab 87: 30403046.[Crossref] [Google Scholar]
  17. Rodriguez L, Graniel J, Ortiz R, , 2007. Effect of leptin on activation and cytokine synthesis in peripheral blood lymphocytes of malnourished infected children. Clin Exp Immunol 148: 478485.[Crossref] [Google Scholar]
  18. Frühbeck G, , 2006. Intracellular signalling pathways activated by leptin. Biochem J 393: 720.[Crossref] [Google Scholar]
  19. Rincón M, , 2001. MAP-kinase signaling pathways in T cells. Curr Opin Immunol 13: 339345.[Crossref] [Google Scholar]
  20. Fantuzzi G, Sennello JA, Batra A, Fedke I, Lehr HA, Zeitz M, Siegmund B, , 2005. Defining the role of T cell-derived leptin in the modulation of hepatic or intestinal inflammation in mice. Clin Exp Immunol 142: 3138.[Crossref] [Google Scholar]
  21. Cerutti A, Puga I, Cols M, , 2012. New helping friends for B cells. Eur J Immunol 42: 19561968.[Crossref] [Google Scholar]
  22. Marie CS, Verkerke HP, Paul SN, Mackey AJ, Petri WA, , 2012. Leptin protects host cells from Entamoeba histolytica cytotoxicity by a STAT3-dependent mechanism. Infect Immun 80: 19341943.[Crossref] [Google Scholar]
  23. Guo X, Roberts MR, Becker SM, Podd B, Zhang Y, Chua SC, Myers MG, Duggal P, Houpt ER, Petri WA, , 2010. Leptin signaling in intestinal epithelium mediates resistance to enteric infection by Entamoeba histolytica . Mucosal Immunol 4: 294303.[Crossref] [Google Scholar]
  24. Allam M, Bertrand R, Zhang-Sun G, Pappas J, Viallet J, , 1997. Cholera toxin triggers apoptosis in human lung cancer cell lines. Cancer Res 57: 26152618. [Google Scholar]
  25. Palacio A, Lopez M, Perez-Bravo F, Monkeberg F, Schlesinger L, , 2002. Leptin levels are associated with immune response in malnourished infants. J Clin Endocrinol Metab 87: 30403046.[Crossref] [Google Scholar]
  26. Keusch GT, Rosenberg IH, Denno DM, Duggan C, Guerrant RL, Lavery JV, Tarr PI, Ward HD, Black RE, Nataro JP, Ryan ET, Bhutta ZA, Coovadia H, Lima A, Ramakrishna B, Zaidi AKM, Burgess DCH, Brewer T, , 2013. Implications of acquired environmental enteric dysfunction for growth and stunting in infants and children living in low- and middle-income countries. Food Nutr Bull 34: 357364.[Crossref] [Google Scholar]
  27. Keusch GT, Denno DM, Black RE, Duggan C, Guerrant RL, Lavery JV, Nataro JP, Rosenberg IH, Ryan ET, Tarr PI, Ward H, Bhutta ZA, Coovadia H, Lima A, Ramakrishna B, Zaidi AKM, Hay Burgess DC, Brewer T, , 2014. Environmental enteric dysfunction: pathogenesis, diagnosis, and clinical consequences. Clin Infect Dis 59 (Suppl 4): S207S212.[Crossref] [Google Scholar]

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  • Received : 02 Mar 2015
  • Accepted : 11 Apr 2015
  • Published online : 05 Aug 2015

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