Differential effects of interleukin-13 on cytomegalovirus and human immunodeficiency virus infection in human alveolar macrophages.
Alveolar macrophages, which form a principal line of defense against a variety of pulmonary pathogens, may themselves be infected by viruses like human immunodeficiency virus-1 (HIV-1), which impair their defensive functions. Interleukin-13 (IL-13), a multifunctional cytokine, has been considered for therapeutic use based on its potent inhibition of HIV-1 in these cells. We have further examined the effects of IL-13 on alveolar macrophages under conditions that reflect those seen in acquired immune deficiency syndrome, where this cell type is often infected by the opportunistic pathogen human cytomegalovirus (HCMV). Alveolar macrophages exposed to both HCMV and HIV-1 consistently exhibited higher levels of HIV-1 replication than cells exposed to HIV-1 alone. HIV-1 production was strongly suppressed in alveolar macrophages treated with IL-13 regardless of whether or not the cultures were coinfected with HCMV. However, IL-13 treatment markedly enhanced the expression of HCMV in otherwise latently infected macrophages in a dose dependent manner. These unexpected differential effects of IL-13 on host-virus interactions are important considerations in guiding its potential therapeutic applications.
Hatch
W C
WC
Division of Experimental Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
Freedman
A R
AR
Boldt-Houle
D M
DM
Groopman
J E
JE
Terwilliger
E F
EF
D017088:AIDS-Related Opportunistic Infections / Q000503:physiopathology / Q000628:therapy / Q000821:virology; D000163:Acquired Immunodeficiency Syndrome / Q000503:physiopathology; D000956:Antigens, Viral / Q000096:biosynthesis; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002478:Cells, Cultured; D003587:Cytomegalovirus / Q000187:drug effects / Q000502:physiology*; D003586:Cytomegalovirus Infections / Q000209:etiology / Q000628:therapy; D004305:Dose-Response Relationship, Drug; D017930:Genes, Reporter; D015497:HIV-1 / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D007700:Kinetics; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000821:virology*; D011994:Recombinant Proteins / Q000096:biosynthesis; D010948:Viral Plaque Assay; D014779:Virus Replication / Q000187:drug effects*; D001616:beta-Galactosidase / Q000032:analysis / Q000096:biosynthesis
D000956:Antigens, Viral; D011994:Recombinant Proteins; D001616:beta-Galactosidase