View Abstract

A6102 - The Effect of HIV Infection on the Upper Respiratory Mucosal Immune Environment
Author Block: S. A. Sellers, K. D. Chason, W. A. Fischer; Pulmonary Diseases and Critical Care Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, NC, United States.
Title:
Authors: SA Sellers, KD Chason, WA Fischer
Institution: The University of North Carolina
Rationale:
Although bacterial and fungal pathogens are well-described as opportunistic infections in individuals infected with human immunodeficiency virus (HIV), respiratory viruses remain poorly understood. Evidence suggests that HIV-infected patients experience a significant burden of viral infections independent of CD4 count including higher mortality and greater rates of hospitalization. The upper respiratory mucosal immune response is the first line of defense of a coordinate antiviral response. We hypothesize that HIV alters the upper respiratory immune environment, similar to its effect on other mucosal surfaces in the body, and that these changes may be implicated in the response to respiratory viral infection.
Methods:
Six HIV-infected individuals with suppressed viral loads, 6 HIV-infected individuals with active viremia and 6 age and gender matched uninfected controls were enrolled. Subjects were ages 18-49, nonsmokers, and otherwise healthy. Subjects filled out health history questionnaires, provided serum samples and underwent nasal mucosal sampling procedures -- epithelial lining fluid (ELF) collection, nasal lavage (NLF) and nasal biopsy. Serum, ELF, and NLF were analyzed using ELISAs targeted at pro-inflammatory cytokines. NLF was analyzed by flow cytometry for nasal-specific immune cells.
Results:
Analysis of the six HIV-infected individuals with undetectable viral loads demonstrated decreased levels of pro-inflammatory cytokines in the nasal mucosa compared to the HIV-uninfected subjects. Specifically, we identified less IL-Iβ, IL-8, IL-16, IL-17α, TNF-α, and TNF-β, and IL-16. This was in contrast to increased systemic inflammation characteristic of HIV-infected patients, indicating that the suppressed inflammatory state of the nasal mucosa is compartmentalized. Additionally, HIV-infected subjects had significantly fewer total immune cells, T-cells, and neutrophils as detected by flow cytometry for CD45, CD3 and CD16 respectively. Analysis of the HIV-infected subjects with viremia is pending.
Conclusion:
We have identified a suppressed mucosal immune environment, including decreased cytokines/chemokines and immune effector cells, in the upper respiratory tract of HIV-infected individuals on ART with suppressed HIV viral loads compared to HIV-uninfected individuals. Further analysis including HIV-infected individuals with active viremia is pending. We hypothesize that this suppression persists in respiratory viral infection leading to an impaired immune response and the observed severity of disease in the HIV-infected population. This immune alteration may also be implicated in the increased risk for other respiratory diseases in the HIV-infected population, including bacterial infections and chronic obstructive pulmonary disease.