Failure of Host Defenses in Human Immunodeficiency Virus

Infection with human immunodeficiency virus (HIV) creates systemic immunosuppression but induces unique alteration of immune functions within lung tissue as well. Cells within the lung, particularly the alveolar macrophage, are important reservoirs of HIV infection. The body's immune response to HIV-infected lung cells creates a persistent inflammatory environment within the alveolar space, which compromises host responses to infectious pathogens. HIV infection alters mucociliary function as well as critical components of airway secretions. Within lung parenchyma, innate and adaptive immune responses to inhaled microorganisms are impaired, including neutrophil influx, lymphocyte responses, and humoral immunity. Collectively, these HIV-induced alterations of host defense explain the increased susceptibility of HIV-infected persons for oropharyngeal candidiasis, bacterial pneumonia, and Pneumocystis jiroveci pneumonia.

KEYWORDS

Host defense against infection - mucociliary function - defensins - collectins - immunoglobulins - alveolar macrophages - dendritic cells - neutrophils - natural killer cells - cytokines - chemokines - CD4⁺ T-lymphocytes - CD8⁺ T-lymphocytes - gamma/delta T-lymphocytes - humoral immunity

REFERENCES

• 1 Davis L, Beck J, Shellito J. Update: HIV infection and pulmonary host defenses.  Semin Respir Infect. 1993;  8 75-85
• 2 Crowe S, Carlin J KS, Lucas C, Hoy J. Predictive value of CD4 lymphocyte numbers for the development of opportunistic infections and malignancies in HIV-infected persons.  J Acquir Immune Defic Syndr. 1991;  4 770-776
• 3 Agostini C, Zambello R, Trentin L, Semenzato G. HIV and pulmonary immune responses.  Immunol Today. 1996;  17 359-364
• 4 Twigg H, Soliman D, Day R et al.. Lymphocytic alveolitis, bronchoalveolar lavage, viral load, and outcome in human immunodeficiency virus infection.  Am J Respir Crit Care Med. 1999;  159 1439-1444
• 5 Wahl S, Orenstein J. Immune stimulation and HIV-1 viral replication.  J Leukoc Biol. 1997;  62 67-71
• 6 Whalen C, Horsburgh C, Hom D, Lahart C, Simberkoff M, Ellner J. Accelerated course of human immunodeficiency virus infection after tuberculosis.  Am J Respir Crit Care Med. 1995;  151 129-135
• 7 Milgrim L M, Rubin J S, Small C B. Mucociliary clearance abnormalities in the HIV-infected patient: a precursor to acute sinusitis [see comment].  Laryngoscope. 1995;  105 1202-1208
• 8 Montella F, Pezzotti P, Di Sora F, Recchia O, Lauria F, Rezza G. Improving the prognostic value of CD4⁺ count using IgA and clinical signs in HIV-seropositive i.v. drug users.  Infection. 1997;  25 117-120
• 9 Fong I, Laurel M, Burford-Mason A. Asymptomatic oral carriage of Candida albicans in patients with HIV infection.  Clin Invest Med. 1997;  20 85-93
• 10 Slavinsky III J, Myers T, Swoboda R K, Leigh J E, Hager S, Fidel Jr P L. Th1/Th2 cytokine profiles in saliva of HIV-positive smokers with oropharyngeal candidiasis.  Oral Microbiol Immunol. 2002;  17 38-43
• 11 Lin A, Johnson D, Patterson T et al.. Salivary anticandidal activity and saliva composition in an HIV-infected cohort.  Oral Microbiol Immunol. 2001;  15 270-278
• 12 Sweet S, Cookson S, Challacombe S. Candida albicans isolates from HIV-infected and AIDS patients exhibit enhanced adherence to epithelial cells.  J Med Microbiol. 1995;  43 452-457
• 13 Ollert M, Wende C, Gorlich M et al.. Increased expression of Candida albicans secretory proteinase, a putative virulence factor, in isolates from human immunodeficiency virus-positive patients.  J Clin Microbiol. 1995;  33 2543-2549
• 14 Wallace J, Hansen N, Lavange L et al.. Respiratory disease trends in the Pulmonary Complications of HIV Infection Study Cohort.  Am J Respir Crit Care Med. 1997;  155 72-80
• 15 Verghese A, al-Samman M, Nabhan D, Naylor A, Rivera M. Bacterial bronchitis and bronchiectasis in human immunodeficiency virus infection.  Arch Intern Med. 1994;  154 2086-2091
• 16 Tsang C, Samaranayake L. Salivary lysozyme and related parameters of a predominantly Chinese, HIV-infected cohort in Hong Kong.  Oral Dis. 1999;  5 241-246
• 17 Mandell I, Barr C, Turgeion L. Longitudinal study of parotid saliva in HIV-1 infection.  J Oral Pathol Med. 1992;  21 209-213
• 18 Muller F, Holberg-Petersen M, Rollag H, Degre M, Brandtzaeg P, Froland S. Nonspecific oral immunity in individuals with HIV infection.  J Acquir Immune Defic Syndr. 1992;  5 46-51
• 19 Zhang L, Yu W, He T et al.. Contribution of human alpha-defensin 1, 2, and 3 to the anti-HIV-1 activity of CD8 antiviral factor.  Science. 2002;  298 995-1000
• 20 Martin W N, Downing J, Williams M, Pasula R, Twigg H, Wright J. Role of sufactant protein A in the pathogenesis of tuberculosis in subjects with human immunodeficiency virus infection.  Proc Assoc Am Physicians. 1995;  107 340-345
• 21 Garred P, Madsen H, Balslev U et al.. Susceptibility to HIV infection and progression of AIDS in relation to vairent alleles of mannose-binding lectin.  Lancet. 1997;  349 236-240
• 22 Margalith M, Levy E, Rinaldo C et al.. HIV-1 IgA specific serum antibodies and disease progression during HVI-1 infection.  J Hum Virol. 2001;  4 269-277
• 23 Cartry O, Moja P, Quesnel A, Pozzetto B, Lucht F, Genin C. Quantification of IgA and IgG and specificities of antibodies to viral proteins in parotid saliva at different stages of HIV-1 infection.  Clin Exp Immunol. 1997;  109 47-53
• 24 Wu X, Jackson S. Plasma and salivary IgA subclasses and IgM in HIV-1-infected individuals.  J Clin Immunol. 2002;  22 106-115
• 25 Agostini C, Zambello R, Trentin L et al.. Prognositc significance of the evaluataion of bronchoalveolar lavage populations in patients with HIV-infection and pulmonary involvement.  Chest. 1991;  100 1601-1606
• 26 Agostini C, Trentin L, Zambello R et al.. Release of GM-CSF by alveolar macrophages in the lung of HIV-1 infected patients: a mechanism accounting for macrophage and neutrophil accumulation.  J Immunol. 1992;  149 3379-3385
• 27 Murray H, Gellen R, Libby D, Rothermel C, Rubin B. Activation of tissue macrophages from AIDS patients: in vitro responses of AIDS alveolar macrophages to lymphokines and gamma interferon.  J Immunol. 1985;  135 2374-2379
• 28 Gordon S, Molyneux M, Boeree M et al.. Opsonic phagocytosis of Streptococcus pneumoniae by alveolar macrophages is not impaired in human immunodeficiency virus-infected Malawian adults.  J Infect Dis. 2001;  184 1345-1349
• 29 Musher D, Watson D, Nickeson D, Gyorkey F, Lahart C, Rossen R. The effect of HIV infection on phagocytosis and killing of Staphylococcus aureus by human pulmonary alveolar macrophages.  Am J Med Sci. 1990;  299 158-163
• 30 Lipman M, Johnson J, Poulter L. Functionally relevant changes in occur in HIV-infected individuals' alveolar macrophages prior to the onset of respiratory disease.  AIDS. 1997;  11 765-772
• 31 Koziel H, Li X, Armstron M, Richards F, Rose R. Alveolar macrophages from human immunodeficiency virus-infected persons demonstrate impaired oxidative burst response to Pneumocystis carinii in vitro.  Am J Respir Cell Mol Biol. 2000;  23 452-459
• 32 Chaturvedi S, Frame P, Newman S. Macrophages from human immunodeficiency virus-positive persons are defective in host defense against Histoplasma capsulatum .  J Infect Dis. 1995;  171 320-327
• 33 Cameron M, Granger D, Matthews T, Weinberg J. Human immunodeficiency virus (HIV)-infected human blood monocytes and peritoneal macrophages have reduced anticryptococcal activity whereas HIV-infected alveolar macrophages retain normal activity.  J Infect Dis. 1994;  170 60-67
• 34 Leong M, Reardon C, Levitz S, Kornfeld H. Human immunodeficiency virus type 1 infection of alveolar macrophages impairs their innate fungicidal activity.  Am J Respir Crit Care Med. 2000;  162 966-970
• 35 Agostini C, Trentin L, Zambello R, Semenzato G. HIV-1 and the lung: infectivity, pathogenic mechanisms, and cellular immune responses taking place in the lower respiratory tract.  Am Rev Respir Dis. 1993;  147 1038-1049
• 36 Orenstein J, Fox C, Wahl S. Macrophages as a source of HIV during opportunistic infections.  Science. 1997;  276 1857-1861
• 37 Lebargy F, Branellec A, Deforges L, Bignon J, Bernaudin J. HIV-1 in human alveolar macrophages from infected patients is latent in vivo but replicates after in vitro stimulation.  Am J Respir Cell Mol Biol. 1994;  10 72-78
• 38 Plata F, Autran B, Martins L P et al.. AIDS virus-specific cytotoxic T lymphocytes in lung disorders.  Nature. 1987;  328 348-351
• 39 Autran B, Mayaud C, Raphael M et al.. Evidence for a cytotoxic T lymphocyte alveolitis in human immunodeficiency virus-infected patients.  AIDS. 1988;  2 179-183
• 40 Chayt K, Harper M, Marselle L et al.. Detection of HTLV-III RNA in lungs of patients with AIDS and pulmonary involvement.  JAMA. 1986;  256 2356-2359
• 41 Lewin S, Krihara J, Sonza S, Irving I, Mills J, Crowe S. HIV-1 DNA and mRNA concentrations are similar in peripheral blood monocytes and alveolar macrophages in HIV-1-infected individuals.  AIDS. 1998;  12 719-727
• 42 Herbein G, Coaquette A, Perez-Bercoff D, Pancino G. Macrophage activation and HIV infection: can the Trojan horse turn into a fortress?.  Curr Mol Med. 2002;  2 723-738
• 43 Gordon S, Read R. Macrophage defences against respiratory tract infections.  Br Med Bull. 2002;  61 45-61
• 44 Sewell A, Price D. Dendritic cells and transmission of HIV.  Trends Immunol. 2001;  22 173-175
• 45 Macatonia S, Lau R, Patterson S, Pinching A, Knight S. Dendritic cell infection, depletion, and dysfunction in HIV-infected individuals.  Immunology. 1990;  71 38-45
• 46 Mason G, Hasimota C, Dickman P, Foutty L, Cobb C. Prognostic implications of bronchoalvelar lavage neutrophilia in patients with Pneumocystis carinii pneumonia and AIDS.  Am Rev Respir Dis. 1989;  139 1336-1342
• 47 Ellis M, Gupta S, Galant S et al.. Impaired neutrophil function in patients with AIDS or AIDS-related complex: a comprehensive evaluation.  J Infect Dis. 1988;  158 1268-1276
• 48 Roilides E, Walsh T, Pizzo P, Rubin M. Granulocyte colony-stimulating factor enhances the phagocytic and bactericidal activity of normal and defective human neutrophils.  J Infect Dis. 1991;  163 579-583
• 49 Murphy P, Lane H, Fauci A, Gallin J. Impairment of neutrophil bactericidal capacity in patients with AIDS.  J Infect Dis. 1988;  158 627-630
• 50 Monari C, Casadevall A, Pietrella D, Bistoni F, Vecchiarelli A. Neutrophils from patients with advanced human immunodeficiency virus infection have impaired complement receptor function and preserved Fc gamma receptor function.  J Infect Dis. 1999;  180 1542-1549
• 51 Gasperini S, Zambello R, Agostini C et al.. Impaired cytokine production by neutrophils isolated from patients with AIDS.  AIDS. 1998;  12 373-379
• 52 Coffey M, Phare S, George S, Peters-Golden M, Kazanjian P. Granulocyte colony-stimulating factor administration to HIV-infected subjects augments reduced leukotriene synthesis and anticryptococcal activity in neutrophils.  J Clin Invest. 1998;  102 663-670
• 53 Mastroianni C, Lichtner M, Mengoni F et al.. Improvement in neutrophil and monocyte function during highly active antiretroviral treatment of HIV-1-infected patients.  AIDS. 1999;  13 883-890
• 54 Sandberg J, Fast N, Palacios E et al.. Selective loss of innate CD4(+) V alpha 24 natural killer T cells in human immunodeficiency virus infection.  J Virol. 2002;  76 7528-7534
• 55 Bruunsgaard H, Pedersen C, Skinhoj P, Pedersen B. Clinical progression of HIV infection: role of NK cells.  Scand J Immunol. 1997;  46 91-95
• 56 Fehniger T, Herbein G, Yu H et al.. Natural killer cells from HIV-1+ patients produced C-C chemokines and inhibit HIV-1 infection.  J Immunol. 1998;  161 6433-6438
• 57 Israel-Biet D, Cadranel J, Beldjord K, Andrieu J, Jeffrey A, Even P. Tumor necrosis factor production in HIV-seropositive subjects: relationship with lung opportunistic infections and HIV expression in alveolar macrophages.  J Immunol. 1991;  147 490-494
• 58 Trentin L, Garbisa S, Zambello R et al.. Spontaneous production of interleukin-6 by alveolar macrophages from human immunodeficiency virus type 1-infected patients.  J Infect Dis. 1992;  166 731-737
• 59 Lipschik G, Doerfler M, Kovacs J et al.. Leukotriene B4 and interleukin-8 in human immunodeficiency virus-related pulmonary disease.  Chest. 1993;  104 763-769
• 60 Wewers M, Diaz P, Wewers M, Lowe M, Nagaraja H, Clanton T. Cigarette smoking in HIV infection induces a suppressive inflammatory environment in the lung.  Am J Respir Crit Care Med. 1998;  158 1543-1549
• 61 Guillon M, Autran B, Denis M et al.. Human immunodeficiency virus related lymphocytic alveolitis.  Chest. 1988;  94 1264-1270
• 62 Agostini C, Zambello R, Trentin L et al.. Cytototoxic events taking place in the lung of patients with HIV infection: evidence for an intrinsic defect of the MHC-unrestricted killing partially restored by the incubation with rIL-2.  Am Rev Respir Dis. 1990;  142 516-522
• 63 Sadal-Sowti B, Parrot A, Quint L, Mayaud C, Debre P, Autran B. Alveolar CD8⁺/CD57⁺ lymphocytes in human immunodeficiency virus infection produce an inhibitor of cytotoxic functions.  Am J Respir Crit Care Med. 1994;  149 972-980
• 64 Twigg H, Spain B, Soliman D et al.. Production of interferon-gamma by lung lymphocytes in HIV-infected individuals.  Am J Physiol. 1999;  276 L256-L262
• 65 Agostini C, Facco M, Siviero M et al.. CXC chemokines IP-10 and Mig expression and direct migration of pulmonary CD8⁺/CXCR3⁺ T cells in the lungs of patients with HIV infection and T-cell alveolitis.  Am J Respir Crit Care Med. 2000;  162 1466-1473
• 66 Spain B, Soliman D, Sidner R, Twigg H. Enhanced proliferation and IL-2 secretion by lung lymphocytes from HIV-infected subjects.  Am J Physiol. 1995;  269 L498-L506
• 67 Autran B, Plata F, Guillon J, Joly P, Mayaud C, Debre P. HIV-specific cytotoxic T lymphocytes directed against alveolar macrophages in HIV-1 infected patients.  Res Virol. 1990;  141 131-136
• 68 Augustin A, Kubo R, Sim G. Resident pulmonary lymphocytes expressing the gamm/delta T-cell receptor.  Nature. 1989;  340 239-241
• 69 Kaufmann S. Gamma/delta and other unconventional lymphocytes: what do they see and what do they do?.  Proc Natl Acad Sci USA. 1996;  93 2272-2279
• 70 Poccia F, Battistini L, Cipriani B et al.. Phosphoantigen-reactive Vdelta9Vdelta2 T lymphocytes suppress in vitro human immunodeficiency virus type 1 replication by cell-released antiviral factors including CC chemokines.  J Infect Dis. 1999;  180 858-861
• 71 Malkovsky M, Wallace M, Fournie J, Fisch P, Poccia F, Gougeon M. Alternative cytotoxic effector mechanisms in infections with immunodeficiency viruses: gamm delta T lymphocytes and natural killer cells.  AIDS. 2000;  14(suppl 3) S175-S186
• 72 Twigg H, Blake A, Soliman D, Bowen L, Heidler K, Wilkes D. Impaired IgG production in the lungs of HIV-infected individuals.  Cell Immunol. 1996;  170 127-133
• 73 Fahy R, Diaz P, Hart J, Wewers M. BAL and serum IgG levels in healthy asymptomatic HIV-infected patients.  Chest. 2001;  119 196-203
• 74 Wallace J, Rao V, Glassroth J et al.. Respiratory illness in persons with human immunodeficiency virus infection.  Am Rev Respir Dis. 1993;  148 1523-1529
• 75 Hirschtick R, Glassroth J, Jordan M et al.. Bacterial pneumonia in patients with HIV infection: pulmonary complications of HIV infection study group.  N Engl J Med. 1995;  333 845-851
• 76 Moore R, Keruly J, Chaisson R. Neutropenia and bacterial infection in acquired immunodeficiency syndrome.  Arch Intern Med. 1995;  155 1965-1970
• 77 Hundt M, Heiken H, Schmidt R. Association of low mannose-binding lectin serum concentrations and bacterial pneumonia in HIV infection.  AIDS. 2000;  14 1853-1876
• 78 Keller D, Breiman R. Preventing bacterial respiratory tract infections among persons infected with human immunodeficiency virus.  Clin Infect Dis. 1995;  21(suppl 1) S77-S83
• 79 Kielhofner M, Atmar R, Hamil R, Musher D. Life-threatening Pseudomonas aeruginosa infections in patients wiht human immunodeficiency virus infection.  Clin Infect Dis. 1992;  14 403-411
• 80 Mitchell D, Miller F. New developments in the pulmonary diseases affecting HIV-infected patients.  Thorax. 1995;  50 294-302
• 81 Verville T D, Huycke M M, Greenfield R A, Fine D P, Kuhls T L, Slater L N. Rhodococcus equi infections of humans. 12 cases and a review of the literature.  Medicine. 1994;  73 119-132
• 82 Uttamchandani R, Daikos G, Reyes R et al.. Nocardiosis in 30 patients with advanced human immunodeficiency virus infection: clinical features and outcome.  Clin Infect Dis. 1994;  18 348-353
• 83 Magnenat J, Nicod L, Auckenthaler R, Junod A. Mode of presentation and diagnosis of bacterial pneumonia in human immunodeficiency virus-infected patients.  Am Rev Respir Dis. 1991;  144 917-922
• 84 Gil Suay V, Cordero P, Martinez E et al.. Parapneumonic effusions secondary to community-acquired bacterial pneumonia in human immunodeficiency virus-infected patients.  Eur Respir J. 1995;  8 1934-1939
• 85 Plouffe J, Breiman R, Facklam R. Bacteremia with Streptococcus pneumoniae .  JAMA. 1996;  275 194-198
• 86 Miller R F, Foley N M, Kessel D, Jeffrey A A. Community acquired lobar pneumonia in patients with HIV infection and AIDS.  Thorax. 1994;  49 367-368
• 87 Gilks C, Ojoo S, Ojoo J et al.. Invasive pneumococcal disease in a cohort of predominantly HIV-1 infected female sex-workers in Nairobi, Kenya.  Lancet. 1996;  347 718-723
• 88 Osmond D, Chin D, Glassroth J et al.. Impact of bacterial pneumonia and Pneumocystis carinii pneumonia on human immunodeficiency virus disease progression. Pulmonary Complications of HIV Study Group.  Clin Infect Dis. 1999;  29 536-543
• 89 Maynaud C, Parrot A, Cadranel J. Pyogenic bacterial lower respiratory tract infection in human immunodeficiency virus-infected patients.  Eur Respir J. 2002;  36 S28-S39
• 90 Masur H, Ognibene F, Yarchoan R et al.. CD4 counts as predictors of opportunistic pneumonias in human immunodeficiency (HIV) infection.  Ann Intern Med. 1989;  111 223-231
• 91 CDC . Guidelines for prophylaxis against Pneumocystis carinii pneumonia for persons infected with human immunodeficiency virus.  MMWR Morb Mortal Wkly Rep. 1989;  38(suppl S-5) 1-9
• 92 Stansell J D, Osmond D H, Charlebois E, et al.. Predictors of Pneumocystis carinii pneumonia in HIV-infected persons. Pulmonary complications of HIV infection study group.  Am J Respir Crit Care Med. 1997;  155 60-66
• 93 Glatt A, Chirgwin K. Pneumocystis carinii pneumonia in human immunodeficiency virus-infected patients.  Arch Intern Med. 1990;  150 271-279
• 94 Ewig S, Bauer T, Schneider C et al.. Clinical characteristics and outcome of Pneumocystis carinii pneumonia in HIV-infected and otherwise immunosuppressed patients.  Eur Respir J. 1995;  8 1548-1553
• 95 Limper A, Offord K, Smith T, Martin W I. Pneumocystis carinii pneumonia: differences in lung parasite number and inflammation in patients with and without AIDS.  Am Rev Respir Dis. 1989;  140 1204-1209
• 96 White D, Gellene R, Gupta S, Cunningham-Rundles C, Stover D. Pulmonary cell populations in the immunosuppressed patient: bronchoalveolar lavage findings during episodes of pneumonitis.  Chest. 1985;  88 352-359
• 97 Smith R L, el-Sadr W M, Lewis M L. Correlation of bronchoalveolar lavage cell populations with clinical severity of Pneumocystis carinii pneumonia.  Chest. 1988;  93 60-64
• 98 Shellito J, Tate C, Ruan S, Kolls J. Murine CD4⁺ T-lymphocytes subsets and host defense against Pneumocystis carinii .  J Infect Dis. 2000;  181 2011-2017
• 99 Hahn P, Limper A. The role of inflammation in respiratory impairment during Pneumocystis carinii pneumonia.  Semin Respir Infect. 2003;  18 40-47
• 100 Benfeld T L, Helweg-Larsen J, Bang D, Junge J, Lundgren J D. Prognostic markers of short-term mortality in AIDS-associated Pneumocystis carinii pneumonia.  Chest. 2001;  119 844-851
• 101 The National Institutes of Health-University of California Expert Panel . Consensus statement on the use of corticosteroids as adjunctive therapy for Pneumocystis pneumonia in the acquired immunodeficiency syndrome.  N Engl J Med. 1990;  323 1500-1504
• 102 Ruan S, Tate C, Lee J, Ritter T, Kolls J, Shellito J. Local delivery of the viral interleukin-10 gene suppresses tissue inflammation in murine Pneumocystis carinii infection.  Infect Immun. 2002;  70 6107-6113