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Glennie, Sarah, Banda, D., Gould, K., Hinds, J., Kamngona, A., Everett, D. D. B., Williams, N. A. and Heyderman, Robert (2013) 'Defective Pneumococcal-Specific Th1 Responses in HIV-Infected Adults Precedes a Loss of Control of Pneumococcal Colonization'. Clinical Infectious Diseases, Vol 56, Issue 2, pp. 291-299.
Full text not available from this repository.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 (HIVneg 13%, HIVasy 19%, and HIVsym 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 HIVneg 26%, HIVasy 30%, HIVsym 31%, HIVART 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.
| Item Type: | Article |
|---|---|
| Subjects: | QU Biochemistry > Cells and Genetics > QU 350 Cellular structures QW Microbiology and Immunology > Immune Responses > QW 700 Infection. Mechanisms of infection and resistance. WC Communicable Diseases > Infection. Bacterial Infections > Bacterial Infections > WC 217 Pneumococcal infections WC Communicable Diseases > Virus Diseases > Acquired Immunodeficiency Syndrome. HIV Infections > WC 503 Acquired immunodeficiency syndrome. HIV infections |
| Faculty: Department: | Clinical Sciences & International Health > Clinical Sciences Department |
| Digital Object Identifer (DOI): | https://doi.org/10.1093/cid/cis842 |
| Depositing User: | Lynn Roberts-Maloney |
| Date Deposited: | 20 Feb 2015 10:25 |
| Last Modified: | 15 Jun 2018 14:43 |
| URI: | https://archive.lstmed.ac.uk/id/eprint/4933 |
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