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Immune Response and Mortality Risk Relate to Distinct Lung Microbiomes in HIV-Pneumonia Patients.

Immune Response and Mortality Risk Relate to Distinct Lung Microbiomes in HIV-Pneumonia Patients.
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Shenoy MK, Iwai S, Lin DL, Worodria W, Ayakaka I, Byanyima P, Kaswabuli S, Fong S, Stone S, Chang E, Davis JL, Faruqi AA, Segal MR, Huang L, Lynch SV,


Shenoy MK, Iwai S, Lin DL, Worodria W, Ayakaka I, Byanyima P, Kaswabuli S, Fong S, Stone S, Chang E, Davis JL, Faruqi AA, Segal MR, Huang L, Lynch SV, (click to view)

Shenoy MK, Iwai S, Lin DL, Worodria W, Ayakaka I, Byanyima P, Kaswabuli S, Fong S, Stone S, Chang E, Davis JL, Faruqi AA, Segal MR, Huang L, Lynch SV,

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American journal of respiratory and critical care medicine 2016 7 22()

Abstract
RATIONALE
The potential role of the airway microbiota in dictating immune responses and infection outcomes in HIV-associated pneumonia is largely unknown.

OBJECTIVE
To investigate whether microbiologically and immunologically distinct subsets of HIV-infected pneumonia patients exist and are related to mortality.

METHODS
Ugandan HIV-infected pneumonia patient (n=182) bronchoalveolar lavage (BAL) samples were obtained at study enrollment (following antibiotic treatment); patient demographics, including 8 and 70 day mortality were collected. Lower airway bacterial community composition was assessed via amplification and sequencing of the V4 region of the 16S rRNA gene. Host immune response gene expression profiles were generated by QPCR using RNA extracted from bronchoalveolar lavage fluid. Liquid and gas chromatography mass spectrometry was used to profile serum metabolites.

MEASUREMENTS AND MAIN RESULTS
Based on airway microbiome composition, the majority of patients segregated into three distinct groups, each of which were predicted to encode metagenomes capable of producing metabolites characteristically enriched in paired serum samples from these patients. These three groups also exhibited differences in mortality; those with the highest rate had increased ceftriaxone administration and culturable Aspergillus, and demonstrated significantly increased induction of airway T-helper 2 responses. The group with the lowest mortality was characterized by increased expression of T-cell immunoglobulin and mucin domain 3 (TIM-3), which down-regulates T-helper 1 pro-inflammatory responses and is associated with chronic viral infection.

CONCLUSIONS
These data provide evidence that compositionally and structurally distinct lower airway microbiomes are associated with discrete local host immune responses, peripheral metabolic reprogramming, and different rates of mortality.

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