Biological parameters of HIV‐1 infection in primary intestinal lymphocytes and macrophages

Mucosal surfaces are the portal of entry for most HIV‐1 infections and play an important role in disease pathogenesis. To characterize the biological parameters of HIV‐1 infection in mucosal cells, we used purified lamina propria lymphocytes and macrophages from normal human small intestine to determine the distribution of the HIV‐1 receptor and coreceptors on intestinal mononuclear cells and the permissiveness of these cells to HIV‐1 infection. Lamina propria lymphocytes expressed CD4, CCR5, and CXCR4. In contrast, lamina propria macrophages expressed CD4 but not CCR5 or CXCR4. Intestinal lymphocytes supported replication by R5 and X4 isolates of HIV‐1, but lamina propria macrophages were permissive to neither. RANTES, macrophage inflammatory protein‐1α (MIP‐1α), and MIP‐1β inhibited infection of intestinal lymphocytes by BaL, indicating that R5 infection of the intestinal lymphocytes was mediated by CCR5. Thus, resident lamina propria lymphocytes, not macrophages, are the target mononuclear cell for HIV‐1 infection in the intestinal mucosa during early HIV‐1 infection.

[1]  M. Russell,et al.  Intestinal Macrophages Lack CD14 and CD89 and Consequently Are Down-Regulated for LPS- and IgA-Mediated Activities1 , 2001, The Journal of Immunology.

[2]  G. Shaw,et al.  Lamina propria lymphocytes, not macrophages, express CCR5 and CXCR4 and are the likely target cell for human immunodeficiency virus type 1 in the intestinal mucosa. , 2000, The Journal of infectious diseases.

[3]  A. Levine,et al.  The differentiated state of intestinal lamina propria CD4+ T cells results in altered cytokine production, activation threshold, and costimulatory requirements. , 1999, Journal of immunology.

[4]  D. Richman,et al.  Sexual transmission and propagation of SIV and HIV in resting and activated CD4+ T cells. , 1999, Science.

[5]  R. Steinman,et al.  Rapid infection of oral mucosal-associated lymphoid tissue with simian immunodeficiency virus. , 1999, Science.

[6]  G. Shaw,et al.  Intestinal macrophages display reduced permissiveness to human immunodeficiency virus 1 and decreased surface CCR5. , 1999, Gastroenterology.

[7]  H. Golding,et al.  Fusion of monocytes and macrophages with HIV-1 correlates with biochemical properties of CXCR4 and CCR5 , 1999, Nature Medicine.

[8]  D. Ho,et al.  In Vivo Distribution of the Human Immunodeficiency Virus/Simian Immunodeficiency Virus Coreceptors: CXCR4, CCR3, and CCR5 , 1998, Journal of Virology.

[9]  R P Johnson,et al.  Gastrointestinal tract as a major site of CD4+ T cell depletion and viral replication in SIV infection. , 1998, Science.

[10]  J. Tse,et al.  Chemokine receptor regulation and HIV type 1 tropism in monocyte-macrophages. , 1998, AIDS research and human retroviruses.

[11]  C. Fox,et al.  Macrophages as a source of HIV during opportunistic infections. , 1997, Science.

[12]  M. Zupancic,et al.  Kinetics of response in lymphoid tissues to antiretroviral therapy of HIV-1 infection. , 1997, Science.

[13]  J. Kearney,et al.  Isolation and purification of CD14-negative mucosal macrophages from normal human small intestine. , 1997, Journal of immunological methods.

[14]  A. Sica,et al.  Bacterial Lipopolysaccharide Rapidly Inhibits Expression of C–C Chemokine Receptors in Human Monocytes , 1997, The Journal of experimental medicine.

[15]  M. Bomsel.  Transcytosis of infectious human immunodeficiency virus across a tight human epithelial cell line barrier , 1997, Nature Medicine.

[16]  Alan S. Perelson,et al.  Quantitative Image Analysis of HIV-1 Infection in Lymphoid Tissue , 1996, Science.

[17]  Phillip D. Smith,et al.  IMMUNOBIOLOGY OF MUCOSAL HIV-1 INFECTION , 1996 .

[18]  R. Steinman,et al.  Replication of HIV-1 in Dendritic Cell-Derived Syncytia at the Mucosal Surface of the Adenoid , 1996, Science.

[19]  W. Strober,et al.  Distinct populations of dendritic cells are present in the subepithelial dome and T cell regions of the murine Peyer's patch , 1996, The Journal of experimental medicine.

[20]  Kees,et al.  Macrophage-tropic variants initiate human immunodeficiency virus type 1 infection after sexual, parenteral, and vertical transmission. , 1994, The Journal of clinical investigation.

[21]  C H Fox,et al.  Quantitative analysis of mononuclear cells expressing human immunodeficiency virus type 1 RNA in esophageal mucosa , 1994, The Journal of experimental medicine.

[22]  D. Ho,et al.  Genotypic and phenotypic characterization of HIV-1 patients with primary infection. , 1993, Science.

[23]  A. Saah,et al.  Relationship of human immunodeficiency virus type 1 sequence heterogeneity to stage of disease. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[24]  M. Raffeld,et al.  Cytomegalovirus induction of tumor necrosis factor-alpha by human monocytes and mucosal macrophages. , 1992, The Journal of clinical investigation.

[25]  B. Korber,et al.  Selective transmission of human immunodeficiency virus type-1 variants from mothers to infants. , 1992, Science.

[26]  H. Balfour,et al.  Human cytomegalovirus-stimulated peripheral blood mononuclear cells induce HIV-1 replication via a tumor necrosis factor-alpha-mediated mechanism. , 1992, The Journal of clinical investigation.

[27]  P. Brandtzaeg.  Overview of the mucosal immune system. , 1989, Current topics in microbiology and immunology.

[28]  Sarah F. Liebschutz,et al.  8. New York , 1987 .

[29]  S. Lee,et al.  Quantitative analysis of total macrophage content in adult mouse tissues. Immunochemical studies with monoclonal antibody F4/80 , 1985, The Journal of experimental medicine.