Abstract

. The main hypothesis to be tested in this proposal is that impairment of alveolar macrophage (AM) functions in AIDS may contribute to the frequency of opportunistic infections including cyrptococcosis. In particular, this proposal seeks to characterize protective responses of normal human alveolar macrophages (AM) to Cryptococcus neoformans and to determine how they may be impaired in AIDS. The work has been divided in several specific aims designed to study 1) the effects of C. neoformans on cytokine expression in AM, 2) the effect of AM-derived cytokines on the ability of AMs to phagocytize and kill C. neoformans, 3) the effects of HIV infection on AM function and ability to clear C. neoformans, and 4) the capacity of C. neoformans to induce HIV expression in AM.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL044846-09
Application #
2771288
Study Section
AIDS and Related Research Study Section 5 (ARRE)
Project Start
1990-04-01
Project End
2000-08-31
Budget Start
1998-09-01
Budget End
1999-08-31
Support Year
9
Fiscal Year
1998
Total Cost
Indirect Cost

  Institution

Name
Boston University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
604483045
City
Boston
State
MA
Country
United States
Zip Code
02118

  Publications

Means, T K; Jones, B W; Schromm, A B et al. (2001) Differential effects of a Toll-like receptor antagonist on Mycobacterium tuberculosis-induced macrophage responses. J Immunol 166:4074-82
Keane, J; Remold, H G; Kornfeld, H (2000) Virulent Mycobacterium tuberculosis strains evade apoptosis of infected alveolar macrophages. J Immunol 164:2016-20
Ieong, M H; Reardon, C C; Levitz, S M et al. (2000) Human immunodeficiency virus type 1 infection of alveolar macrophages impairs their innate fungicidal activity. Am J Respir Crit Care Med 162:966-70
Koziel, H; Kim, S; Reardon, C et al. (1999) 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 160:2048-55
Wu, P; Phillips, M I; Bui, J et al. (1998) Adeno-associated virus vector-mediated transgene integration into neurons and other nondividing cell targets. J Virol 72:5919-26
Nau, G J; Guilfoile, P; Chupp, G L et al. (1997) A chemoattractant cytokine associated with granulomas in tuberculosis and silicosis. Proc Natl Acad Sci U S A 94:6414-9
Reardon, C C; Kim, S J; Wagner, R P et al. (1996) Phagocytosis and growth inhibition of Cryptococcus neoformans by human alveolar macrophages: effects of HIV-1 infection. AIDS 10:613-8
Reardon, C C; Kim, S J; Wagner, R P et al. (1996) Interferon-gamma reduces the capacity of human alveolar macrophages to inhibit growth of Cryptococcus neoformans in vitro. Am J Respir Cell Mol Biol 15:711-5
Harrison, T S; Kornfeld, H; Levitz, S M (1995) The effect of infection with human immunodeficiency virus on the anticryptococcal activity of lymphocytes and monocytes. J Infect Dis 172:665-71
Sugar, A M; Picard, M; Wagner, R et al. (1995) Interactions between human bronchoalveolar macrophages and Blastomyces dermatitidis conidia: demonstration of fungicidal and fungistatic effects. J Infect Dis 171:1559-62

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