Impaired mucociliary
clearance (MCC) is a hallmark of acquired chronic airway diseases like chronic
bronchitis associated with chronic obstructive pulmonary disease (COPD) and
asthma. This manifests as microbial colonization of the lung consequently
leading to recurrent respiratory infections.
People living with HIV demonstrate
increased incidence of these chronic airway diseases. Bacterial pneumonia
continues to be an important comorbidity in people living with HIV even though
anti-retroviral therapy has succeeded in restoring CD4+ cell counts. People
living with HIV demonstrate increased microbial colonization of the lower airways.
The microbial flora is similar to that observed in diseases like cystic
fibrosis and COPD suggesting that mucociliary dysfunction could be a
contributing factor to the increased incidence of chronic airway diseases in
people living with HIV.
The three principal components of the MCC apparatus
are, a mucus layer, ciliary beating, and a periciliary airway surface liquid
(ASL) layer that facilitates ciliary beating. Cystic fibrosis transmembrane
conductance regulator (CFTR) plays a pivotal role in regulating the periciliary
ASL. HIV proteins can suppress all the components of the MCC apparatus by
increasing mucus secretion and suppressing CFTR function. This can decrease ASL
height leading to suppressed ciliary beating. The effects of HIV on MCC are
exacerbated when combined with other aggravating factors like smoking or
inhaled substance abuse, which by themselves can suppress one or more
components of the MCC system.
This review discusses the pathophysiological
mechanisms that lead to MCC suppression in people living with HIV who also
smoke tobacco or abuse illicit drugs.
Below: (A) HIV Tat induces expression of TGF-β1 mRNA with a concomitant decrease in CFTR mRNA levels. NHBE ALI cultures re-differentiated at the air liquid interface were treated with recombinant Clade B Tat (10 nM: *p < 0.05) apically and basolaterally. Total RNA was isolated and TGF-β1 and CFTR mRNA levels were quantitated by qRT-PCR. HIV Tat induces almost a 1.7-fold increase in TGF-β1 mRNA expression. This translates to a significant decrease in CFTR mRNA levels. Data are mean ± SE of three experiments from three different lungs. (B) Nationwide trends in Cigarette smoking and drug abuse in general population compared with people living with HIV. While the trend in addiction is similar between the two, the proportion of people living with HIV who smoke cigarettes or abuse street drugs is significantly than that observed in the general population. Cigarette smoking is the most prevalent addiction [62.5% smokers (Benard et al., 2007; Lifson et al., 2010; Lifson and Lando, 2012) compared to 17.8% nationwide], followed by Marijuana [29% (Woolridge et al., 2005) compared to 7.5% nationwide], Cocaine [22.5% (Hinkin et al.,2004) compared to 0.6% nationwide] and methamphetamine [11% (Mitchell et al., 2006) compared to 0.2% nationwide]. The data for substance abuse in the general population is obtained from http://www.drugabuse.gov/national-survey-drug-use-health.
Full article at: http://goo.gl/q4vIqB
Department of
Immunology, Herbert Wertheim College of Medicine, Florida International
University, Miami, FL, USA
Edited by: Pankaj Seth, National Brain Research Centre,
India
Reviewed by: Hidekatsu Iha, Oita University, Japan;
Yoshitaka Sato, Nagoya University Graduate School of Medicine, Japan
*Correspondence: Hoshang J. Unwalla, Department of
Immunology, Herbert Wertheim College of Medicine, Florida International
University, 11200 SW 8th Street, AHC-1 #421, Miami, FL 33199, USA ; Email: ude.uif@allawnuh
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