Chronic helminth infection induces alternatively activated macrophages expressing high levels of CCR5 with low interleukin-12 production and Th2-biasing ability
Por:
Rodríguez-Sosa M., Satoskar A.R., Calderón R., Gomez-Garcia L., Saavedra R., Bojalil R., Terrazas L.I.
Publicada:
1 ene 2002
Resumen:
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 E2 (PGE2) 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 PGE2 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-?), contrary to macrophages from acute infections. Blockade of B7-2 and IL-6 and inhibition of PGE2 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.
Filiaciones:
Rodríguez-Sosa M.:
Department of Immunology, Instituto Nacional de Cardiologia, Juan Badiano #1, Tlalpan, D.F. Mexico 14080, Mexico
Satoskar A.R.:
Department of Immunology, Instituto Nacional de Cardiologia, Juan Badiano #1, Tlalpan, D.F. Mexico 14080, Mexico
Calderón R.:
Department of Immunology, Instituto Nacional de Cardiologia, Juan Badiano #1, Tlalpan, D.F. Mexico 14080, Mexico
Gomez-Garcia L.:
Department of Immunology, Instituto Nacional de Cardiologia, Juan Badiano #1, Tlalpan, D.F. Mexico 14080, Mexico
Saavedra R.:
Department of Immunology, Instituto Nacional de Cardiologia, Juan Badiano #1, Tlalpan, D.F. Mexico 14080, Mexico
Bojalil R.:
Department of Immunology, Instituto Nacional de Cardiologia, Juan Badiano #1, Tlalpan, D.F. Mexico 14080, Mexico
Terrazas L.I.:
Department of Immunology, Instituto Nacional de Cardiologia, Juan Badiano #1, Tlalpan, D.F. Mexico 14080, Mexico
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