Peripheral Cytokine Responses toTrichuris murisReflect Those Occurring Locally at the Site of Infection

Abstract

The study of human cellular immune responses to parasite infection under field conditions is very complex. Often, the only practical site from which to sample the cellular responses is the peripheral blood. Sampling peripheral blood lymphocytes (PBL) relies on the assumption that these peripheral responses accurately reflect the immune responses acting locally at the site of infection. This is a particularly important point for the human intestinal helminthTrichuris trichiura, which solely inhabits the cecum and large intestine and so will stimulate a localized immune response. Using the well-defined model ofT. trichiura,T. murisin the mouse, we have demonstrated that the dominant cytokine responses of the mesenteric lymph nodes (MLN) can be detected by sampling PBL. Resistant mice which mount a type 2 cytokine response in their MLN had PBL producing interleukin-4 (IL-4), IL-5, and IL-9, with negligible levels of gamma interferon (IFN-γ). Conversely, susceptible mice which mount a type 1 cytokine response in their MLN had PBL producing IFN-γ and negligible levels of type 2 cytokines. We have also shown that the PBL are capable of mounting a functional immune response againstT. muris. PBL from immune mice were capable of transferring immunity toT. muris-infected severe combined immunodeficient (C.B-17scid/scid) mice. Sampling PBL responses is therefore a viable option for monitoring human intestinal immune responses duringT. trichiurainfection in the field.