Reduced apoptosis in BALB/c mice infected with Heligmosomoides polygyrus

Abstract

We evaluated levels of apoptosis and the immune response ex vivo in BALB/c mice infected with Heligmosomoides polygyrus. Cell proliferation, apoptosis and cytokine production were measured in mesenteric lymph nodes (MLN) without exposure to H. polygyrus antigens in culture. The inhibited apoptosis and cytokine production reported might reflect a state of cell hyporesponsiveness in the prepatent phase of infection. These changes were accompanied by changes in the percentage of CD4+ cells in MLN and popliteal lymph nodes (PLN). The prolonged reduction in apoptosis coexisted with induced cell proliferation, elevated TNF-alpha, IL-12p70, IFN-gamma, IL-6, IL-10 and TGF-beta synthesis, but lowered IL-4 and IL-2 levels. In the chronic phase of infection an increasing production of IFN-gamma, monocyte chemotactic protein-1 (MCP-1), IL-10 and TGF-beta with decreasing concentrations of other cytokines resulted in restored apoptosis. The cytokine response in serum showed moderate production of TNF-alpha, temporary involvement of IL-12p70, induction of IFN-gamma and IL-10 synthesis, as well as growing IL-6 and MCP-1 production. It is suggested that a synchronized synthesis of distinct cytokines is accompanied by different levels of inhibited apoptosis during the prepatent and chronic phases of H. polygyrus infection in BALB/c mice. We suggest that immunosuppression provoked by the nematode is not the outcome of parasite-induced apoptosis, but rather results from a hyporesponsiveness experienced by cells during H. polygyrus infection.