IAI Accepts, published online ahead of print on 17 March 2008

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Infect. Immun. doi:10.1128/IAI.00094-08
Copyright (c) 2008, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

A role for nitric oxide in hookworm associated immune suppression

Blaise Dondji, Richard D. Bungiro, Lisa M. Harrison, Jon J. Vermeire, Carlo Bifulco, Diane McMahon-Pratt, and Michael Cappello^*

Departments of Pediatrics, Pathology, Microbial Pathogenesis, and Epidemiology & Public Health, Yale University School of Medicine, New Haven, CT 06520 USA

^* To whom correspondence should be addressed. Email: michael.cappello{at}yale.edu.

Hookworm infection is a major cause of anemia and malnutrition in resource poor countries. Human and animal studies suggest that infection with these intestinal nematodes is associated with impaired cellular immunity, characterized by reduced lymphocyte proliferation in response to both parasite and heterologous antigens. We report here data from studies aimed at defining mechanisms through which hookworms modulate the host cellular immune response. Splenocytes and mesenteric lymph node (MLN) cells from hamsters infected with Ancylostoma ceylanicum showed minimal proliferation in response to mitogen at days 20 and 30 post infection (PI) with partial recovery noted at day 70 PI. The proliferative capacity of enriched splenocyte T cell preparations from infected animals following stimulation with hookworm antigens was partially restored in the presence of antigen presenting cells from uninfected hamsters. Analysis by FACS revealed that hookworm infection is associated with reduced percentages of both CD4+ and surface IgG+ lymphocytes in the spleen and MLN cells. Splenocytes from infected hamsters also secreted more nitric oxide (NO) in culture than those from naïve animals. Inhibition of NO secretion was associated with partial restoration of the proliferative capacity of splenocytes from infected animals in response to ConA, suggesting a role for NO in mediating this effect. Together, these data demonstrate that hookworm infection is associated with impaired function of antigen presenting cells and depletion of important lymphocyte subpopulations, and also suggests a role for NO in parasite-induced immunosupression.