Innate immune responses induced by Chlamydia pneumoniae infection

Magdalenić, Vjera (2005). Innate immune responses induced by Chlamydia pneumoniae infection. PhD thesis The Open University.

DOI: https://doi.org/10.21954/ou.ro.000101b6

Abstract

In the current project innate immune responses to C. pneumoniae infection were studied, using a human in vitro model: a combination of lung epithelial cell lines (HEp-2 and A549) and primary blood-derived monocyte-derived macrophages (MdMs). The experiments were designed with a view to identify the host-pathogen interactions early in the infection that may lead to persistence and the development of chronic diseases such as atherosclerosis.

Infected epithelial cells and MdMs released IL-8 and IL-6, while MdMs also released IL-1β, TNF-α and IL-10, but not IL-12. The release of cytokines by infected cells was modulated by IL-17 treatment. Infected MdMs, but not infected epithelial cells displayed an altered surface phenotype: CD14, CD40 and CD54 were up-regulated, whereas MHC class I and II, and CD45 were down-regulated. Medium derived from infected epithelial cells modulated surface profile of MdMs in a different manner: MHC class I and II, and CD91 were up-regulated, while CD14 and CD45 were down-regulated.

IFN-γ plays a key role in controlling chlamydial growth through induction of indoleamine 2,3-dioxygenase (IDO). A549 cells were found not to control chlamydial growth although they inducibly expressed IDO mRNA. The expression of Suppressor of Cytokine Signalling 3 (SOCS3) was investigated and A549 cells constitutively expressed both SOCS3 mRNA and protein, while HEp-2 cells expressed only SOCS3 mRNA. SOCS3 expression was further up-regulated by infection in both cells. IFN-γ treatment of A549 cells did not up-regulate SOCS3 mRNA expression, but did so in HEp-2 cells. The intracellular mechanisms of inhibition of IFN-γ-mediated chlamydial control in these cells remained unclear and require further study.

The findings presented in this thesis are discussed in relation to a hypothesis that early immune responses of infected lung cells play a crucial role in the outcome of the infection and that they contribute to the establishment of persistence.

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