Peripheral cytokine responses to Trichuris muris reflect those occurring locally at the site of infection - PubMed (original) (raw)

Peripheral cytokine responses to Trichuris muris reflect those occurring locally at the site of infection

M D Taylor et al. Infect Immun. 2000 Apr.

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-gamma). Conversely, susceptible mice which mount a type 1 cytokine response in their MLN had PBL producing IFN-gamma 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.

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Figures

FIG. 1

Type 2 cytokine production by BALB/K MLNC (A, C, and E) and PBL (B, D, and F) taken at various time points p.i. and restimulated in vitro with T. muris E/S Ag (n = 4 for each time point). Day 0 refers to uninfected control animals. In panels A, C, and E, solid lines show median values and circles represent individual animals. PBL at all time points, and MLNC at day 0, were pooled within groups.

FIG. 2

Type 2 cytokine production by AKR MLNC (A to C) and IL-4 production by AKR PBL (D) taken at various time points p.i. and restimulated in vitro with T. muris E/S Ag (n = 4 for each time point except for uninfected controls, where n = 3). Day 0 refers to uninfected control animals. In panels A to C, solid lines show median values and circles represent individual animals. PBL at all time points, and MLNC at day 0, were pooled within groups.

FIG. 3

IFN-γ production by AKR MLNC and PBL (A and B, respectively) and BALB/K MLNC and PBL (C and D, respectively) taken at various time points p.i. and restimulated in vitro with T. muris E/S Ag. In panels A and C, solid lines show median values and circles refer to individual animals. PBL at all time points, and MLNC at day 0, were pooled within groups; n = 4 for BALB/K time points and for all AKR time points except for the uninfected controls at day 0, where n = 3.

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Peripheral cytokine responses to Trichuris muris reflect those occurring locally at the site of infection - PubMed (original) (raw)