Advertisement

Lung microbiome in human immunodeficiency virus infection

      The lung microbiome plays a significant role in normal lung function and disease. Because microbial colonization is likely influenced by immunodeficiency, one would speculate that infection with human immunodeficiency virus (HIV) alters the lung microbiome. Furthermore, how this alteration might impact pulmonary complications now seen in HIV-infected patients on antiretroviral therapy (ART), which has shifted from opportunistic infections to diseases associated with chronic inflammation, is not known. There have been limited publications on the lung microbiome in HIV infection, many of them emanating from the Lung HIV Microbiome Project. Current evidence suggests that the lung microbiome in healthy HIV-infected individuals with preserved CD4 counts is similar to uninfected individuals. However, in individuals with more advanced disease, there is an altered alveolar microbiome characterized by a loss of richness and evenness (alpha diversity) within individuals. Furthermore, as a group the taxa making up the HIV-infected and uninfected lung microbiome are different (differences in beta diversity), and the HIV-infected population is more spread out (greater dispersion) than the uninfected population. These differences decline with ART, but even after effective therapy the alveolar microbiome in HIV-infected individuals contains increased amounts of signature bacteria, some of which have previously been associated with chronic lung inflammation. Furthermore, more recent investigations into the lung virome in HIV infection suggest that perturbations in lung viral communities also exist in HIV infection, and that these too are associated with evidence of lung inflammation. Thus, it is likely both microbiome and virome alterations in HIV infection contribute to lung inflammation in these individuals, which has important implications on the changing spectrum of pulmonary complications in patients living with HIV.

      Abbreviations:

      NIH (National Institutes of Health), HIV (human immunodeficiency virus), LHMP (Lung Human Microbiome Project), ART (antiretroviral therapy), AM (alveolar macrophage), BAL (bronchoalveolar lavage), COPD (chronic obstructive lung disease), OTU (operational taxonomic unit), DNA (deoxyribonucleic acid), RNA (ribonucleic acid), PBMCs (peripheral blood mononuclear cells)
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Translational Research
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Erb-Downward J.R.
        • Thompson D.L.
        • Han M.K.
        • et al.
        Analysis of the lung microbiome in the “healthy” smoker and in COPD.
        PLoS One. 2011; 6: e16384
        • Morris A.
        • Beck J.M.
        • Schloss P.D.
        • et al.
        Comparison of the respiratory microbiome in healthy nonsmokers and smokers.
        Am J Respir Crit Care Med. 2013; 187: 1067-1075
        • Twigg 3rd, H.L.
        • Morris A.
        • Ghedin E.
        • et al.
        Use of bronchoalveolar lavage to assess the respiratory microbiome: signal in the noise.
        Lancet Respir Med. 2013; 1: 354-356
        • Lozupone C.
        • Cota-Gomez A.
        • Palmer B.E.
        • et al.
        Widespread colonization of the lung by Tropheryma whipplei in HIV infection.
        Am J Respir Crit Care Med. 2013; 187: 1110-1117
        • Zemanick E.T.
        • Sagel S.D.
        • Harris J.K.
        The airway microbiome in cystic fibrosis and implications for treatment.
        Curr Opin Pediatr. 2011; 23: 319-324
        • Grubb J.R.
        • Moorman A.C.
        • Baker R.K.
        • Masur H.
        The changing spectrum of pulmonary disease in patients with HIV infection on antiretroviral therapy.
        AIDS. 2006; 20: 1095-1107
        • Twigg 3rd, H.L.
        • Knox K.S.
        HIV-Related Lung Disorders.
        Drug Discov Today Dis Mech. 2007; 4: 95-101
        • Buhl R.
        • Jaffe H.A.
        • Holroyd K.J.
        • et al.
        Activation of alveolar macrophages in asymptomatic HIV-infected individuals.
        J Immunol. 1993; 150: 1019-1028
        • Day R.B.
        • Wang Y.
        • Knox K.S.
        • et al.
        Alveolar macrophages from HIV-infected subjects are resistant to Mycobacterium tuberculosis in vitro.
        Am J Respir Cell Mol Biol. 2004; 30: 403-410
        • Barry S.M.
        • Johnson M.A.
        • Janossy G.
        Increased proportions of activated and proliferating memory CD8+ T lymphocytes in both blood and lung are associated with blood HIV viral load.
        J Acquir Immune Defic Syndr. 2003; 34: 351-357
        • Franchini M.
        • Walker C.
        • Henrard D.R.
        • et al.
        Accumulation of activated CD4+ lymphocytes in the lung of individuals infected with HIV accompanied by increased virus production in patients with secondary infections.
        Clin Exp Immunol. 1995; 102: 231-237
        • Twigg 3rd, H.L.
        Bronchoalveolar lavage fluid in HIV-infected patients. “Cytokine soup”.
        Chest. 1993; 104: 659-661
        • Agostini C.
        • Poletti V.
        • Zambello R.
        • et al.
        Phenotypical and functional analysis of bronchoalveolar lavage lymphocytes in patients with HIV infection.
        Am Rev Respir Dis. 1988; 138: 1609-1615
        • Brenchley J.M.
        • Knox K.S.
        • Asher A.I.
        • et al.
        High frequencies of polyfunctional HIV-specific T cells are associated with preservation of mucosal CD4 T cells in bronchoalveolar lavage.
        Mucosal Immunol. 2008; 1: 49-58
        • Neff C.P.
        • Chain J.L.
        • MaWhinney S.
        • et al.
        Lymphocytic alveolitis is associated with the accumulation of functionally impaired HIV-specific T cells in the lung of antiretroviral therapy-naive subjects.
        Am J Respir Crit Care Med. 2015; 191: 464-473
        • Jambo K.C.
        • Sepako E.
        • Fullerton D.G.
        • et al.
        Bronchoalveolar CD4+ T cell responses to respiratory antigens are impaired in HIV-infected adults.
        Thorax. 2011; 66: 375-382
        • Tardif M.R.
        • Tremblay M.J.
        LFA-1 is a key determinant for preferential infection of memory CD4+ T cells by human immunodeficiency virus type 1.
        J Virol. 2005; 79: 13714-13724
        • Kalsdorf B.
        • Scriba T.J.
        • Wood K.
        • et al.
        HIV-1 infection impairs the bronchoalveolar T-cell response to mycobacteria.
        Am J Respir Crit Care Med. 2009; 180: 1262-1270
        • Fahy R.J.
        • Diaz P.T.
        • Hart J.
        • Wewers M.D.
        BAL and serum IgG levels in healthy asymptomatic HIV-infected patients.
        Chest. 2001; 119: 196-203
        • Gordon S.B.
        • Miller D.E.
        • Day R.B.
        • et al.
        Pulmonary immunoglobulin responses to Streptococcus pneumoniae are altered but not reduced in human immunodeficiency virus-infected Malawian adults.
        J Infect Dis. 2003; 188: 666-670
        • Eagan R.
        • Twigg 3rd, H.L.
        • French N.
        • et al.
        Lung fluid immunoglobulin from HIV-infected subjects has impaired opsonic function against pneumococci.
        Clin Infect Dis. 2007; 44: 1632-1638
        • Takahashi H.
        • Oishi K.
        • Yoshimine H.
        • et al.
        Decreased serum opsonic activity against Streptococcus pneumoniae in human immunodeficiency virus-infected Ugandan adults.
        Clin Infect Dis. 2003; 37: 1534-1540
        • Twigg 3rd, H.L.
        • Weiden M.
        • Valentine F.
        • et al.
        Effect of highly active antiretroviral therapy on viral burden in the lungs of HIV-infected subjects.
        J Infect Dis. 2008; 197: 109-116
        • Twigg 3rd, H.L.
        • Knox K.S.
        Impact of antiretroviral therapy on lung immunology and inflammation.
        Clin Chest Med. 2013; 34: 155-164
        • Cribbs S.K.
        • Fontenot A.P.
        The Impact of Antiretroviral Therapy on Lung Immunology.
        Semin Respir Crit Care Med. 2016; 37: 157-165
        • Twigg 3rd, H.L.
        • Day R.B.
        • Schnizlein-Bick C.T.
        • et al.
        Effect of Highly Active Antiretroviral Therapy (HAART) on Pulmonary Lymphocyte Phenotype.
        Am J Respir Crit Care Med. 2006; 173: A476
        • Twigg 3rd, H.L.
        • Day R.B.
        • Smith P.A.
        • Knox K.S.
        Highly Active Antiretroviral Therapy (HAART) Markedly Decreases Bronchoalveolar Lavage (BAL) Chemokine Concentrations.
        Am J Respir Cell Mol Biol. 2007; 175: 248A
        • Morris A.
        • Crothers K.
        • Beck J.M.
        • Huang L.
        • American Thoracic Society Committee on HIVPD
        An official ATS workshop report: Emerging issues and current controversies in HIV-associated pulmonary diseases.
        Proc Am Thorac Soc. 2011; 8: 17-26
        • Murray J.F.
        • Garay S.M.
        • Hopewell P.C.
        • et al.
        NHLBI workshop summary. Pulmonary complications of the acquired immunodeficiency syndrome: an update. Report of the second National Heart, Lung and Blood Institute workshop.
        Am Rev Respir Dis. 1987; 135: 504-509
        • Murray J.F.
        • Mills J.
        Pulmonary infectious complications of human immunodeficiency virus infection. Part II.
        Am Rev Respir Dis. 1990; 141: 1582-1598
        • Murray J.F.
        • Mills J.
        Pulmonary infectious complications of human immunodeficiency virus infection. Part I.
        Am Rev Respir Dis. 1990; 141: 1356-1372
        • Iwai S.
        • Fei M.
        • Huang D.
        • et al.
        Oral and airway microbiota in HIV-infected pneumonia patients.
        J Clin Microbiol. 2012; 50: 2995-3002
        • Iwai S.
        • Huang D.
        • Fong S.
        • et al.
        The lung microbiome of Ugandan HIV-infected pneumonia patients is compositionally and functionally distinct from that of San Franciscan patients.
        PLoS One. 2014; 9: e95726
        • Spor A.
        • Koren O.
        • Ley R.
        Unravelling the effects of the environment and host genotype on the gut microbiome.
        Nat Rev Microbiol. 2011; 9: 279-290
        • Brenchley J.M.
        • Price D.A.
        • Schacker T.W.
        • et al.
        Microbial translocation is a cause of systemic immune activation in chronic HIV infection.
        Nat Med. 2006; 12: 1365-1371
        • Beck J.M.
        • Schloss P.D.
        • Venkataraman A.
        • et al.
        Multi-center comparison of lung and oral microbiomes of HIV-infected and HIV-uninfected individuals.
        Am J Respir Crit Care Med. 2015; 192: 1335-1344
        • Cribbs S.K.
        • Uppal K.
        • Li S.
        • et al.
        Correlation of the lung microbiota with metabolic profiles in bronchoalveolar lavage fluid in HIV infection.
        Microbiome. 2016; 4: 3
        • Twigg 3rd, H.L.
        • Knox K.S.
        • Zhou J.
        • et al.
        Effect of advanced HIV infection on the respiratory microbiome.
        Am J Respir Crit Care Med. 2016; 194: 226-235
        • Lundgren J.D.
        • Babiker A.G.
        • Gordin F.
        • et al.
        Initiation of Antiretroviral Therapy in Early Asymptomatic HIV Infection.
        N Engl J Med. 2015; 373: 795-807
        • Danel C.
        • Moh R.
        • Gabillard D.
        • et al.
        A Trial of Early Antiretrovirals and Isoniazid Preventive Therapy in Africa.
        N Engl J Med. 2015; 373: 808-822
        • Janoff E.N.
        • Breiman R.F.
        • Daley C.L.
        • Hopewell P.C.
        Pneumococcal disease during HIV infection. Epidemiologic, clinical, and immunologic perspectives.
        Ann Intern Med. 1992; 117: 314-324
        • Dewhirst F.E.
        • Chen T.
        • Izard J.
        • et al.
        The human oral microbiome.
        J Bacteriol. 2010; 192: 5002-5017
        • Segal L.N.
        • Alekseyenko A.V.
        • Clemente J.C.
        • et al.
        Enrichment of lung microbiome with supraglottic taxa is associated with increased pulmonary inflammation.
        Microbiome. 2013; 1: 19
        • van Sighem A.I.
        • Gras L.A.
        • Reiss P.
        • Brinkman K.
        • de Wolf F.
        Life expectancy of recently diagnosed asymptomatic HIV-infected patients approaches that of uninfected individuals.
        AIDS. 2010; 24: 1527-1535
        • Crothers K.
        • Huang L.
        • Goulet J.L.
        • et al.
        HIV infection and risk for incident pulmonary diseases in the combination antiretroviral therapy era.
        Am J Respir Crit Care Med. 2011; 183: 388-395
        • Aberg J.A.
        Aging, inflammation, and HIV infection.
        Top Antivir Med. 2012; 20: 101-105
        • Deeks S.G.
        • Verdin E.
        • McCune J.M.
        Immunosenescence and HIV.
        Curr Opin Immunol. 2012; 24: 501-506
        • Appay V.
        • Sauce D.
        Immune activation and inflammation in HIV-1 infection: causes and consequences.
        J Pathol. 2008; 214: 231-241
        • Davalos A.R.
        • Coppe J.P.
        • Campisi J.
        • Desprez P.Y.
        Senescent cells as a source of inflammatory factors for tumor progression.
        Cancer Metastasis Rev. 2010; 29: 273-283
        • Coppe J.P.
        • Patil C.K.
        • Rodier F.
        • et al.
        Senescence-associated secretory phenotypes reveal cell-nonautonomous functions of oncogenic RAS and the p53 tumor suppressor.
        PLoS Biol. 2008; 6: 2853-2868
        • Effros R.B.
        • Allsopp R.
        • Chiu C.P.
        • et al.
        Shortened telomeres in the expanded CD28-CD8+ cell subset in HIV disease implicate replicative senescence in HIV pathogenesis.
        AIDS. 1996; 10: F17-F22
        • Orenstein J.M.
        • Fox C.
        • Wahl S.M.
        Macrophages as a source of HIV during opportunistic infections.
        Science. 1997; 276: 1857-1861
        • Koziel H.
        • Kim S.
        • Reardon C.
        • et al.
        Enhanced in vivo human immunodeficiency virus-1 replication in the lungs of human immunodeficiency virus-infected persons with Pneumocystis carinii pneumonia.
        Am J Respir Crit Care Med. 1999; 160: 2048-2055
        • Chang Y.
        • Cesarman E.
        • Pessin M.S.
        • et al.
        Identification of herpesvirus-like DNA sequences in AIDS-associated Kaposi's sarcoma.
        Science. 1994; 266: 1865-1869
        • Stevens S.J.
        • Blank B.S.
        • Smits P.H.
        • Meenhorst P.L.
        • Middeldorp J.M.
        High Epstein-Barr virus (EBV) DNA loads in HIV-infected patients: correlation with antiretroviral therapy and quantitative EBV serology.
        AIDS. 2002; 16: 993-1001
        • Naeger D.M.
        • Martin J.N.
        • Sinclair E.
        • et al.
        Cytomegalovirus-specific T cells persist at very high levels during long-term antiretroviral treatment of HIV disease.
        PLoS One. 2010; 5: e8886
        • Springer K.L.
        • Weinberg A.
        Cytomegalovirus infection in the era of HAART: fewer reactivations and more immunity.
        J Antimicrob Chemother. 2004; 54: 582-586
        • Minot S.
        • Bryson A.
        • Chehoud C.
        • et al.
        Rapid evolution of the human gut virome.
        Proc Natl Acad Sci U S A. 2013; 110: 12450-12455
        • Young J.C.
        • Chehoud C.
        • Bittinger K.
        • et al.
        Viral metagenomics reveal blooms of anelloviruses in the respiratory tract of lung transplant recipients.
        Am J Transplant. 2015; 15: 200-209
        • Wylie K.M.
        • Mihindukulasuriya K.A.
        • Zhou Y.
        • et al.
        Metagenomic analysis of double-stranded DNA viruses in healthy adults.
        BMC Biol. 2014; 12: 71
        • Huffnagle G.B.
        • Noverr M.C.
        The emerging world of the fungal microbiome.
        Trends Microbiol. 2013; 21: 334-341
        • Nguyen L.D.
        • Viscogliosi E.
        • Delhaes L.
        The lung mycobiome: an emerging field of the human respiratory microbiome.
        Front Microbiol. 2015; 6: 89
        • Cui L.
        • Morris A.
        • Ghedin E.
        The human mycobiome in health and disease.
        Genome Med. 2013; 5: 63
        • Cui L.
        • Lucht L.
        • Tipton L.
        • et al.
        Topographic diversity of the respiratory tract mycobiome and alteration in HIV and lung disease.
        Am J Respir Crit Care Med. 2015; 191: 932-942