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Inhibition of phago‐lysosome fusion by chlamydial elementary bodies is necessary for the early induction of type I IFNs in mouse macrophages
Author(s) -
Nagarajan Uma M,
Wyrick Priscilla B,
Rank Roger G
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.675.24
Subject(s) - biology , endosome , chlamydiae , chlamydia , innate immune system , chlamydiaceae , microbiology and biotechnology , lysosome , virology , immunology , immune system , biochemistry , enzyme , intracellular
Two strains of Chlamydia, the mouse Chlamydia muridarum (MoPn) and the guinea pig Chlamydia caviae (GPIC) have equivalent growth rates in epithelial cells while only MoPn grows effectively in macrophages. To determine the early gene expression differences in mouse macrophages to these 2 organisms, micro array analysis was performed from RNA collected 3h post infection, followed by confirmation by real‐time quantitative RT‐PCR. Uninfected cells and cells treated with UV‐inactivated MoPn or GPIC were used as controls. Expression of pro‐inflammatory cytokines TNF‐α, IL‐6, IL1β, and inhibin β‐A expression were similar in GPIC or MoPn infected macrophages. However, only MoPn infection induced the expression of type I IFN and IFN response genes such as Egr‐1, IP‐10, and Gem GTPases. These responses were not observed in GPIC‐infected macrophages, or in UV‐inactivated MoPn and GPIC. To address the role of early bacterial and host interaction in the differences in gene expression, the infected macrophages were studied by electron microscopy (EM). EM analyses show the presence of intact chlamydial elementary bodies (EB) and reticulate bodies (RB) in endosomes of MoPn‐infected macrophages after 2h. In contrast, the GPIC EB's ended up in phagocytic vacuoles suggesting these EBs were killed. These data suggest that escape of MoPn chlamydial EB from lysosomal fusion is critical for the initiation of type I IFNs and IFN response genes. Further, these data suggest that induction of type I IFNs could be mediated by innate receptors interacting with the early endosomes containing chlamydiae.