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 7

Dominant effect of L. major on the local tissue microenvironment.

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Dominant effect of L. major on the local tissue microenvironment. ...
(A) BALB/c mice were injected with OVA/IFA in one ear and infected with L. major in the contralateral ear. Two weeks later, mice were challenged with CpG for 30 hours and cells were isolated for detection of cytokine production ex vivo by ELISPOT. *P = 0.04 for difference in increase in the number of IL-4–producing cells between the ear tissue infected with L. major and challenged with CpG and the ear tissue infected with L. major alone (Student’s t test); P ≤ 0.03 for the differences between IFN-γ–producing cells in the ear tissue infected with L. major and challenged with CpG and ear tissue immunized with OVA/IFA and challenged with CpG (Student’s t test). nd, not detectable. (B) OVA-specific cells in L. major–infected or OVA/CFA-immunized ear tissue 30 hours after in vivo challenge with OVA/CpG determined by ELISPOT as in A. *P ≤ 0.03 for the difference in OVA-specific IFN-γ–producing cells between ear tissue infected with L. major and challenged with OVA/CpG and OVA/CFA plus OVA/CpG-immunized ear (Student’s t test). Data are representative of at least 3 independent experiments.