Peripheral Cytokine Responses to Trichuris muris Reflect Those Occurring Locally at the Site of Infection

Abstract

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 helminth Trichuris trichiura , which solely inhabits the cecum and large intestine and so will stimulate a localized immune response. Using the well-defined model of T. trichiura , T. muris in 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 against T. muris . PBL from immune mice were capable of transferring immunity to T. muris -infected severe combined immunodeficient (C.B-17 scid/scid ) mice. Sampling PBL responses is therefore a viable option for monitoring human intestinal immune responses during T. trichiura infection in the field.