Silencing or permanent activation: host-cell responses in models of persistent Chlamydia pneumoniae infection

Abstract

SummaryChlamydia pneumoniae causes respiratory infections. In chronic diseases associated with Chlamydia , such as arteriosclerosis, C. pneumoniae is present in a persistent form, which might participate in pathogenesis of chronic inflammatory disease. To elucidate how these intracellular bacteria modulate host-cells during persistence, we compared the expression pattern of a range of host genes after short (24 h) and long (up to 7 days) times of chlamydia infection in HeLa-cells. One day post infection, in three cellculture models of persistence, namely treatment with penicillin or IFN-g g g g , or iron-depletion, infection induced the genes of CTGF, IL-6, IL-8, IL-11, LIF, EGR-1 and ETV4 in a similar fashion. However, after a longer time, two modes of host-cell reaction emerged that were dependent on the persistence model used. After IFN-g g g g and penicillin treatment chlamydia-induced host-cell gene expression was inhibited, while it stayed upregulated in iron-depletion. Human monocytes/macrophages, in which persistence naturally occurs, were additionally investigated: for several genes, UV-inactivated and viable chlamydia caused long-lasting upregulation. Thus, this study reveals (i) the ability of C. pneumoniae to participate in two putative pathomechanisms of persistence, silencing and permanent activation, which might represent different in vivo situations and (ii) a strong dependence on the mode of persistence induction.

Transcriptional Response Patterns ofChlamydophila psittaciin Different In Vitro Models of Persistent Infection

“…On the other hand, the effect of persistent chlamydial infection on the host cell response was also found to be dependent on the inducing reagent. While IFN-␥ and penicillin treatment led to inhibition of C. pneumoniae-induced gene expression in HeLa cells, continuous and even increasing responses were observed with the iron depletion model (29).…”

Kinematics of Intracellular Chlamydiae Provide Evidence for Contact-Dependent Development

“…We explored this part of the hypothesis using C. trachomatis grown in the presence of penicillin. Penicillin-exposed chlamydial cultures are known to produce aberrantly enlarged mRBs and provide a model for chlamydial persistence, a hallmark of chlamydial chronic infection and disease in humans (1,2,4,25). In our experiments, cultures were supplemented with penicillin G at 24 hpi and observed at 48 hpi, allowing for inclusions to contain a mixture of persistent mRBs as well as normal RBs, IBs, and EBs.…”

“…Coincidental to the morphological change, expression of stress response genes is upregulated (e.g., hsp60) while expression of genes thought to be involved in late differentiation (e.g., omcB) is blocked (5,6,13). Because mRBs may be kept in culture for several weeks (except for phage-induced stress) and removal of the stressor "unlocks" development and allows re-sumption of late differentiation to EBs, the stress response of the chlamydiae is thought to represent a suitable in vitro model for persistent infection (1,2,4,25).…”

Chlamydophila pneumoniae phospholipase D (CpPLD) drives Th17 inflammation in human atherosclerosis

“…Productive infection is not the only possible outcome of C. pneumoniae interaction with host cells. Persistence due to nutritional deprivation, antibiotic treatment, or immune reaction leads to a chronic or latent infection characterized by the presence of abnormal RB that fail to mature (5). Some aspects of the developmental cycle of C. pneumoniae suggest a direct implication of PLD in pathogenesis, specifically by affecting the regulation of lipid metabolism and lipid exchange between C. pneumoniae and host cells.…”