Helminth infections induce Th2-type biased immune responses. Although the mechanisms involved in this phenomenonare 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-␥), 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.

Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine that is involved in the host

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