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 withTaenia crassicepsas 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 PGE₂and 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-γ), contrary to macrophages from acute infections. Blockade of B7-2 and IL-6 and inhibition of PGE₂failed 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 pleiotropic cytokine produced by the pituitary gland and multiple cell types, including macrophages (Mø), dendritic cells (DC) and T-cells. Upon releases MIF modulates the expression of several inflammatory molecules, such as TNF-α, nitric oxide and cyclooxygenase 2 (COX-2). These important MIF characteristics have prompted investigators to study its role in parasite infections. Several reports have demonstrated that MIF plays either a protective or deleterious role in the immune response to different pathogens. Here, we review the role of MIF in the host defense response to some important protozoan infections.

In recent years, there has been a significant increase in the study of own and foreign human factors favoring the development of different types of cancer, including genetic and environmental ones. However, the fact that the immune response plays a fundamental role in the development of immunity and susceptibility to colorectal cancer (CRC) is much stronger. Among the many cell populations of the immune system that participate in restricting or favoring CRC development, regulatory T cells (Treg) play a major role in orchestrating immunomodulation during CRC. In this review, we established concrete evidence supporting the fact that Treg cells have an important role in the promotion of tumor development during CRC, mediating an increasing suppressive capacity which controls the effector immune response, and generating protection for tumors. Furthermore, Treg cells go through a process called “phenotypic plasticity”, where they co-express transcription factors that promote an inflammatory profile. We reunited evidence that describes the interaction between the different effector populations of the immune response and its modulation by Treg cells adapted to the tumor microenvironment, including the mechanisms used by Treg cells to suppress the protective immune response, as well as the different subpopulations of Treg cells participating in tumor progression, generating susceptibility during CRC development. Finally, we discussed whether Treg cells might or might not be a therapeutic target for an effective reduction in the morbidity and mortality caused by CRC.

IL-18 has been shown to play a critical role in the development of a Th1 response and immunity against intracellular pathogens. To determine the role of IL-18 in the development of protective immunity against Leishmania major, we have analyzed the course of cutaneous L. major in IL-18-deficient C57BL/6 mice (IL-18^−/−) compared with similarly infected wild-type mice (IL-18^+/+). After L. major infection, IL-18^−/− mice may develop larger lesions during early phase of infection but eventually will resolve them as efficiently as IL-18^+/+ mice. By 2 wk after infection, although Ag-stimulated lymph node cells from L. major-infected IL-18^+/+ and IL-18^−/− mice produced similar levels of IFN-γ, those from IL-18^−/− mice produced significantly more IL-12 and IL-4. By 10 wk after infection, both IL-18^+/+ and IL-18^−/− mice had resolved L. major infection. At this time, lymph node cells from both IL-18^+/+ and IL-18^−/− mice produced IL-12 and IFN-γ but no IL-4. Furthermore, administration of anti-IFN-γ Abs to IL-18^−/− mice rendered them susceptible to L. major. These results indicate that despite the role IL-18 may play in early control of cutaneous L. major lesion growth, this cytokine is not critical for development of protective Th1 response and resolution of L. major infection.

To determine the role of endogenous migration inhibitory factor (MIF) in regulation of immune response during murine cysticercosis caused by the helminth parasiteTaenia crassiceps, we analyzed the course ofT. crassicepsinfection in MIF^−/−BALB/c mice. MIF^−/−mice were highly susceptible toT. crassicepsand developed significantly higher parasite loads compared to similarly infected MIF^+/+mice. Throughout the course of infection,Taenia crassicepssoluble antigen-stimulated spleen cells from both MIF^+/+and MIF^−/−mice produced significant and comparable levels of interleukin-4 (IL-4), but those from MIF^−/−mice produced significantly more IL-13, as well as gamma interferon (IFN-γ), suggesting that the susceptibility of MIF^−/−mice toT. crassicepswas not due to the lack of IFN-γ production. Interestingly, low levels of both total and specific immunoglobulin G2a were observed in MIF^−/−cysticercotic mice despite the high IFN-γ levels; in addition, peritoneal macrophages obtained fromT. crassiceps-infected MIF^−/−mice at different time points failed to respond efficiently to stimulation in vitro with lipopolysaccharide plus IFN-γ and produced significantly lower levels of IL-12, tumor necrosis factor alpha, and NO compared to those from MIF^+/+mice. These findings demonstrate that MIF plays a critical role in mediating protection againstT. crassicepsin vivo. Moreover, these findings also suggest that impaired macrophage function rather than the lack of Th1 development may be responsible for mediating susceptibility toT. crassiceps.