title: Chronic helminth infection induces alternatively activated macrophages expressing high levels of CCR5 with low interleukin-12 production and Th2-biasing ability.
abstract: Helminth infections induce Th2-type biased immune responses. Although the mechanisms involved in this phenomenon are not yet clearly defined, antigen-presenting cells (APC) could play an important role in this process. Here, we have used peritoneal macrophages (F4/80+) recruited at different times after challenge with Taenia crassiceps as APC and tested their ability to regulate Th1/Th2 differentiation. Macrophages from acute infections produced high levels of interleukin-12 (IL-12) and nitric oxide (NO), paralleled with low levels of IL-6 and prostaglandin E(2) (PGE(2)) and with the ability to induce strong antigen-specific CD4+ T-cell proliferation in response to nonrelated antigens. In contrast, macrophages from chronic infections produced higher levels of IL-6 and PGE(2) and had suppressed production of IL-12 and NO, associated with a poor ability to induce antigen-specific proliferation in CD4+ T cells. Failure to induce proliferation was not due to a deficient expression of accessory molecules, since major histocompatibility complex class II, CD40, and B7-2 were up-regulated, together with CD23 and CCR5 as infection progressed. These macrophages from chronic infections were able to bias CD4+ T cells to produce IL-4 but not gamma interferon (IFN-gamma), contrary to macrophages from acute infections. Blockade of B7-2 and IL-6 and inhibition of PGE(2) failed to restore the proliferative response in CD4+ T cells. Furthermore, studies using STAT6(-/-) mice revealed that STAT6-mediated signaling was essential for the expansion of these alternatively activated macrophages. These data demonstrate that helminth infections can induce different macrophage populations that have Th2-biasing properties.
authors.affiliation: Department of Immunology, Instituto Nacional de Cardiologia Ignacio Chavez, D.F. Mexico 14080, Mexico.
authors.forename: Miriam
authors.initials: M
authors.lastname: Rodríguez-Sosa
authors.forename: Abhay R
authors.initials: AR
authors.lastname: Satoskar
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Calderón
authors.forename: Lorena
authors.initials: L
authors.lastname: Gomez-Garcia
authors.forename: Rafael
authors.initials: R
authors.lastname: Saavedra
authors.forename: Rafael
authors.initials: R
authors.lastname: Bojalil
authors.forename: Luis I
authors.initials: LI
authors.lastname: Terrazas
mesh_terms: D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D015703:Antigens, CD / Q000276:immunology; D018122:B7-1 Antigen / Q000276:immunology; D051940:B7-2 Antigen; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002455:Cell Division; D002478:Cells, Cultured; D002908:Chronic Disease; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology; D015232:Dinoprostone / Q000276:immunology; D005260:Female; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D018664:Interleukin-12 / Q000096:biosynthesis*; D015850:Interleukin-6 / Q000276:immunology; D008262:Macrophage Activation / Q000276:immunology*; D017737:Macrophages, Peritoneal / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D019713:Receptors, CCR5 / Q000096:biosynthesis*; D050800:STAT6 Transcription Factor; D013621:Taenia / Q000276:immunology; D013622:Taeniasis / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology*; D013997:Time Factors; D015534:Trans-Activators / Q000235:genetics / Q000276:immunology
chemical_list: D015703:Antigens, CD; D018122:B7-1 Antigen; D051940:B7-2 Antigen; C497965:Cd86 protein, mouse; D016207:Cytokines; D000949:Histocompatibility Antigens Class II; D015850:Interleukin-6; D008562:Membrane Glycoproteins; D019713:Receptors, CCR5; D050800:STAT6 Transcription Factor; C494100:Stat6 protein, mouse; D015534:Trans-Activators; D018664:Interleukin-12; D015232:Dinoprostone