Among patients with human immunodeficiency virus (HIV), pulmonary complications are a common cause of morbidity and mortality. Although bacterial and fungal pathogens are well-described, respiratory viruses remain poorly understood. Evidence suggests viruses represent a significant disease burden. Compared to HIV-uninfected patients, HIV-infected patients experience a greater incidence of viral infections independent of CD4 count, higher mortality, and greater rates of hospitalization. We sought to elicit the mechanism by characterizing the effect of HIV on the respiratory epithelium, the initial target of respiratory viruses.
Six HIV-infected patients and 6 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.
Decreased levels of pro-inflammatory cytokines were identified at the respiratory mucosa of HIV-infected subjects. We identified less IL-Iβ, IL-8, IL-5, and IL-16 in ELF and NLF. This is 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.
The mechanism underlying the morbidity and mortality of respiratory viruses in HIV-infected patients is unclear. However, we identified that respiratory epithelial cells, which initiate the mucosal immune response, demonstrate a suppressed inflammatory state in HIV-infected subjects. We hypothesize that this suppression persists in viral infection leading to an impaired immune response and prolonged respiratory virus replication, contributing to the observed burden of disease in this population.
W. Fischer II, None