title: Defective pneumococcal-specific Th1 responses in HIV-infected adults precedes a loss of control of pneumococcal colonization.
abstract: BACKGROUND
  African adults infected with human immunodeficiency virus (HIV) have high rates of pneumococcal colonization and invasive disease. Here we have investigated the possibility that HIV disrupts the normal balance of pneumococcal-specific helper T cell (Th) 1/Th17 immunity to colonization, resulting in a more permissive nasopharyngeal niche.
  
  
  METHODS
  One hundred thirty-six HIV-infected and -uninfected Malawian adults were enrolled in the study. Changes in rates and composition of nasopharyngeal pneumococcal colonization were analyzed using microarray. The underlying pneumococcal-specific Th1/Th17 responses associated with altered pneumococcal colonization were investigated using flow cytometry.
  
  
  RESULTS
  We find that pneumococcal carriage is only modestly increased in asymptomatic HIV-infected Malawian adults but that colonization rates rise dramatically during symptomatic disease (HIV(neg) 13%, HIV(asy) 19%, and HIV(sym) 38%). These rates remain high in subjects established on antiretroviral therapy (ART): 33% (at 6-12 months) and 52% (at 18 months), with HIV-infected individuals carrying a broader range of invasive and noninvasive serotypes compared with HIV-negative controls. The frequency of multiple serotype carriage (>1 serotype HIV(neg) 26%, HIV(asy) 30%, HIV(sym) 31%, HIV(ART) 31%) is not affected. These changes in colonization are associated with generalized CD4 T-cell depletion, impaired antigen-specific proliferation, and a defect in pneumococcal-specific T-cell interferon-γ but not interleukin 17 production.
  
  
  CONCLUSIONS
  These data reveal the persistently poor control of pneumococcal colonization in HIV-infected adults following immune ART-mediated reconstitution, highlighting a potential reservoir for person-to-person spread and vaccine escape. Novel approaches to control colonization either through vaccination or through improvements in the quality of immune reconstitution are required.
authors.affiliation: Malawi-Liverpool-Wellcome Trust Clinical Research Programme, University of Malawi College of Medicine, Blantyre, Malawi. sarah.glennie@liverpool.ac.uk
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Glennie
authors.forename: Dominic
authors.initials: D
authors.lastname: Banda
authors.forename: Kate
authors.initials: K
authors.lastname: Gould
authors.forename: Jason
authors.initials: J
authors.lastname: Hinds
authors.forename: Arox
authors.initials: A
authors.lastname: Kamngona
authors.forename: Dean D B
authors.initials: DD
authors.lastname: Everett
authors.forename: Neil A
authors.initials: NA
authors.lastname: Williams
authors.forename: Robert S
authors.initials: RS
authors.lastname: Heyderman
mesh_terms: D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D060085:Coinfection / Q000276:immunology*; D015169:Colony Count, Microbial; D018450:Disease Progression; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D020381:Interleukin-17 / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D008875:Middle Aged; D011008:Pneumococcal Infections / Q000276:immunology* / Q000382:microbiology*; D013296:Streptococcus pneumoniae / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology*; D055815:Young Adult
chemical_list: D020381:Interleukin-17; D007371:Interferon-gamma