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P1‐327: Analysis of Chlamydia pneumoniae‐infected monocytes following incubation with a novel peptide, acALY18: A potential treatment for infection in Alzheimer's disease
Author(s) -
Balin Brian J.,
Thacker James D.,
Caruthers Corey M.,
Hingley Susan T.,
Ruszak Elizabeth K.,
Zoga Juliana D.,
Appelt Denah M.
Publication year - 2010
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2010.05.880
Subject(s) - biology , innate immune system , immune system , neuroinflammation , immunology , acquired immune system , immunity , chlamydophila pneumoniae , chlamydia , inflammation , virology , chlamydiales
Our laboratory has been studying the role of infection with the obligate intracellular bacterium, Chlamydia pneumoniae, in sporadic late-onset Alzheimer disease (LOAD). This infection may be a trigger for the pathology observed in LOAD as a function of initiating neuroinflammation following entry of the organism into the brain. We have hypothesized that one entry mechanism may be by blood-borne infected monocytes trafficking the infection into the brain. Our current studies focus on infection of monocytes in vitro followed by analysis of infection using immunofluorescence labeling and RTPCR-microarray techniques. In addition, we are studying a novel approach utilizing a unique peptide, acALY-18, derived from the endogenously expressed endoplasmic reticulum protein TRPC1, to eradicate the organism at 24-48 hr post-infection, thereby limiting its capacity to develop into a chronic/persistent infection. The peptide appears to stimulate the innate immune system through activation of the inflammasome. Results: C. pneumoniae prominently and stably infected THP1 monocytes at 24-48hr. Numerous large inclusions were labeled using specific anti-chlamydial monoclonal antibodies. Monocyte gene expression, both for markers of innate and adaptive immunity as well as for Alzheimer disease, was significantly altered.For example, 6 genes were up-regulated at least 10 fold as compared to 4 genes down-regulated to the same extent the immunity array at 48hr post-infection. In the Alzheimer's array, 16 genes were up-regulated at least 4 fold as compared to 2 that were down-regulated to the same extent. Intriguingly, following incubation of C. pneumoniae-infected cells with acALY18 peptide (25-50nM) at 24hr post-infection, there was a dramatic clearance of the organism from the monocytes (80% infected and untreated to 13-15% infected after treatment). Furthermore, gene regulation was altered following peptide treatment, as there were 13 genes that were up-regulated at least 10 fold and no genes were down-regulated to that extent in the immunity array. . Conclusions: Our data suggest that C. pneumoniae-infected monocytes are altered significantly to promote a chronic/persistent infection that may account for the presence of C. pneumoniae in LOAD. Furthermore, stimulating the innate immune response using the novel peptide, acALY18, promotes clearance of C. pneumoniae from infected monocytes; this peptide may be a viable candidate for treating C. pneumoniae infections in Alzheimer disease.