Pathogen-imposed skewing of mouse chemokine and cytokine expression at the infected tissue site
Shoshana D. Katzman, Deborah J. Fowell
Shoshana D. Katzman, Deborah J. Fowell
Published January 10, 2008
Citation Information: J Clin Invest. 2008;118(2):801-811. https://doi.org/10.1172/JCI33174.
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Research Article Immunology

Pathogen-imposed skewing of mouse chemokine and cytokine expression at the infected tissue site

Abstract

Compartmentalization of immunity ensures tight regulation of T cell activation in the LN and precise effector T cell delivery to inflamed sites. Herein we show that the tissue-specific accumulation of effector T cells can be subverted by a pathogen at the infection site. Using the Leishmania major mouse model of dermal infection, we observed a restricted chemokine profile at the infection site, i.e., the expression of Th2 cell–attracting CCL7 but not of Th1 cell–attracting chemokines. Consistent with these chemokine expression data, recruitment of cytokine-producing T cells to the infection site was also selective. Both IL-4– and IFN-γ–producing effector T cells homed to inflamed OVA/CFA-immunized dermis, but only IL-4–producing cells homed to L. major–infected dermis. The narrowing of the cytokine repertoire at the site of infection with L. major was driven, in part, by pathogen-induced CCL7. Inflammatory signals failed to disrupt the early restrictive L. major infection site, which suggests that L. major dominantly modifies the local milieu. We have highlighted an emerging principle in pathogen-host interactions: that the cytokine repertoire at the infection site and the LN draining the infection site can be different because of the ability of the pathogen to modify the chemokine profile at the infection site. Thus, pathogens may edit the LN cytokine repertoire through differential recruitment of cytokine-producing cells.

Authors

Shoshana D. Katzman, Deborah J. Fowell

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Figure 3

Selective recruitment of cytokine effectors to the early L. major–infected ear dermis.

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Selective recruitment of cytokine effectors to the early L. major–infect...
(A) Experimental design of OVA-specific recruitment studies. (B) Two weeks after infection/immunization of BALB/c mice, OVA-specific cytokine production was determined after in vitro restimulation with 5 μM pOVA by ELISPOT (antigen-specific spots/106 for LN and total spots/ear). Left: OVA-specific cytokine response in the dLN from the OVA/CFA immunized ear and from the LN draining the L. major–infected ear. Right: OVA-specific cytokine response in the ear of mice 30 hours after challenge with OVA protein, 2 weeks after infection of ear pinna with L. major or immunization of ear tissue with OVA/CFA. Fewer than 10 OVA-specific cytokine-secreting cells in the L. major–infected ear tissue were detected before OVA challenge. Data are representative of results from 4 comparable experiments. *P = 0.008 for differences in IL-4/IFN-γ ratio between OVA/L. major–infected ear tissue and OVA/CFA-immunized ear tissue as determined by Student’s t test. Similar results were obtained when C57BL/6 mice were used in the recruitment studies as in A. (C) BALB/c mice were treated as in A, except the L. major–infected ear tissue was challenged with OVA/CFA, and OVA-specific recruitment to the ear was -analyzed as in B. Data are representative of results from 3 independent experiments.