title: Chronic HIV infection enhances the responsiveness of antigen presenting cells to commensal Lactobacillus.
abstract: Chronic immune activation despite long-term therapy poses an obstacle to immune recovery in HIV infection. The role of antigen presenting cells (APCs) in chronic immune activation during HIV infection remains to be fully determined. APCs, the frontline of immune defense against pathogens, are capable of distinguishing between pathogens and non-pathogenic, commensal bacteria. We hypothesized that HIV infection induces dysfunction in APC immune recognition and response to some commensal bacteria and that this may promote chronic immune activation. Therefore we examined APC inflammatory cytokine responses to commensal lactobacilli. We found that APCs from HIV-infected patients produced an enhanced inflammatory response to Lactobacillus plantarum WCFS1 as compared to APCs from healthy, HIV-negative controls. Increased APC expression of TLR2 and CD36, signaling through p38-MAPK, and decreased expression of MAP kinase phosphatase-1 (MKP-1) in HIV infection was associated with this heightened immune response. Our findings suggest that chronic HIV infection enhances the responsiveness of APCs to commensal lactobacilli, a mechanism that may partly contribute to chronic immune activation.
authors.affiliation: Department of Medical Microbiology and Immunology, University of California Davis, Davis, California, United States of America.
authors.forename: Lauren H
authors.initials: LH
authors.lastname: Nagy
authors.forename: Irina
authors.initials: I
authors.lastname: Grishina
authors.forename: Monica
authors.initials: M
authors.lastname: Macal
authors.forename: Lauren A
authors.initials: LA
authors.lastname: Hirao
authors.forename: William K
authors.initials: WK
authors.lastname: Hu
authors.forename: Sumathi
authors.initials: S
authors.lastname: Sankaran-Walters
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Gaulke
authors.forename: Richard
authors.initials: R
authors.lastname: Pollard
authors.forename: Jennifer
authors.initials: J
authors.lastname: Brown
authors.forename: Maria
authors.initials: M
authors.lastname: Suni
authors.forename: Andreas J
authors.initials: AJ
authors.lastname: Baumler
authors.forename: Smita
authors.initials: S
authors.lastname: Ghanekar
authors.forename: Maria L
authors.initials: ML
authors.lastname: Marco
authors.forename: Satya
authors.initials: S
authors.lastname: Dandekar
mesh_terms: D000328:Adult; D000368:Aged; D000938:Antigen-Presenting Cells / Q000276:immunology*; D018955:CD36 Antigens / Q000378:metabolism; D002908:Chronic Disease; D015331:Cohort Studies; D003713:Dendritic Cells / Q000378:metabolism; D005260:Female; D015658:HIV Infections / Q000097:blood* / Q000201:enzymology / Q000276:immunology* / Q000382:microbiology; D006801:Humans; D007109:Immunity / Q000276:immunology; D007249:Inflammation / Q000097:blood / Q000276:immunology / Q000473:pathology; D007778:Lactobacillus / Q000276:immunology*; D020935:MAP Kinase Signaling System; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism; D010766:Phosphorylation; D011971:Receptors, Immunologic / Q000378:metabolism; D051195:Toll-Like Receptor 2 / Q000378:metabolism; D055815:Young Adult; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D018955:CD36 Antigens; D011971:Receptors, Immunologic; C495342:TLR2 protein, human; D051195:Toll-Like Receptor 2; D048051:p38 Mitogen-Activated Protein Kinases
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