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 4

Local control of cytokine responses within the infected ear dermis.

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Local control of cytokine responses within the infected ear dermis. (A) ...
(A) BALB/c OVA-primed CD4 T cells were isolated from the dLN 2 weeks after OVA/CFA immunization of mice and were transferred to BALB/c TCR Cα–/– recipients injected with L. major or OVA/CFA 2 weeks before cell transfer. OVA-specific cytokine production by donor LN cells (before transfer) and ears of recipients was determined 30 hours after in vivo OVA protein challenge by in vitro antigen-specific ELISPOT. P = 0.024 for the change in the ratio of cytokine-secreting cells between L. major–infected ears challenged with OVA and OVA/CFA-immunized ears. Data are representative of 3 independent experiments. (B) T cell transfers as in A with OVA-primed whole CD4 (black bars) or CD4+CD25– (gray bars) cells isolated from the dLN and transferred to L. major–infected or OVA/CFA-immunized BALB/c TCR Cα–/– recipients 2 weeks after infection or immunization. OVA-specific cytokine production by donor LN cells and recipient ears 30 hours after in vivo OVA protein challenge by in vitro antigen-specific ELISPOT. Data are representative of 2 independent experiments.