title: Suppression of human immunodeficiency virus type 1 replication in macrophages by commensal bacteria preferentially stimulating Toll-like receptor 4.
abstract: Protection from primary human immunodeficiency virus type 1 (HIV-1) infection has not yet been accomplished by vaccines inducing HIV-1-specific acquired immunity. Nevertheless, it has been reported that a small subgroup of women remain resistant to HIV-1 infection under natural conditions. If similar conditions can be induced in uninfected individuals, it will contribute the first line of protection against HIV-1 infection, and also improve the effects of anti-HIV-1 vaccines. We reasoned that innate immunity may be involved in the resistance to HIV-1 infection, and investigated the effects of various Toll-like receptor (TLR) ligands and commensal bacteria on HIV-1 replication in macrophages, one of the initial targets of HIV-1 infection and also the main mediators of innate immunity. We established the HIV-1 reporter monocytic cell line, THP-1/NL4-3luc, which could be differentiated into macrophage-like cells in vitro. In these cells, stimulation of TLR3 and TLR4 by their ligands suppressed HIV-1 expression partly through type I interferon (IFN). Among the commensal bacteria tested, Escherichia coli, Veillonella parvula and Neisseria mucosa suppressed HIV-1 expression, whereas Lactobacillus acidophilus, Prevotella melaninogenica, P. bivia and Mycobacterium smegmatis enhanced it. The bacteria with suppressive effects preferentially stimulated TLR4, whereas the ones with enhancing effects stimulated TLR2. Neutralizing antibodies against TLR4 and IFN-α/β receptor abrogated bacterially mediated HIV-1 suppression. Suppressive effects of E. coli, V. parvula and N. mucosa on HIV-1 replication were reproducible in primary monocyte-derived macrophages following acute HIV-1 infection. These findings suggest that certain commensal bacteria preferentially stimulating TLR4 potentially produce local environments resistant to HIV-1 infection.
authors: Department of Immunotherapeutics, Graduate School, Tokyo Medical and Dental University, Tokyo, Japan.
authors: Nursarat
authors: N
authors: Ahmed
authors: Takaya
authors: T
authors: Hayashi
authors: Atsuhiko
authors: A
authors: Hasegawa
authors: Hiroyuki
authors: H
authors: Furukawa
authors: Noboru
authors: N
authors: Okamura
authors: Toshio
authors: T
authors: Chida
authors: Takao
authors: T
authors: Masuda
authors: Mari
authors: M
authors: Kannagi
mesh_terms: D001419:Bacteria / Q000254:growth & development* / Q000276:immunology*; D002460:Cell Line; D002470:Cell Survival; D017930:Genes, Reporter; D015497:HIV-1 / Q000254:growth & development*; D006801:Humans; D007370:Interferon Type I / Q000276:immunology; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D008264:Macrophages / Q000382:microbiology* / Q000821:virology*; D051195:Toll-Like Receptor 2 / Q000276:immunology; D051196:Toll-Like Receptor 3 / Q000276:immunology; D051197:Toll-Like Receptor 4 / Q000276:immunology*; D014779:Virus Replication
chemical_list: D007370:Interferon Type I; C495342:TLR2 protein, human; C495344:TLR3 protein, human; C495345:TLR4 protein, human; D051195:Toll-Like Receptor 2; D051196:Toll-Like Receptor 3; D051197:Toll-Like Receptor 4; D008156:Luciferases