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

No abstract

During helminthic infections, strong Th2 type-biased responses concomitant with impaired cell-proliferative responses to parasitic and unrelated antigens are major immunological hallmarks. Parasite glycan structures have been proposed to play a role in modulating these responses. To understand early events related to immune modulation during cestode infection, we have examined the role of intact glycans of antigens from Taenia crassiceps in the recruitment of innate cells. Soluble antigens from this cestode contained higher levels of carbohydrates than proteins. Intraperitoneal injection of the antigens rapidly recruited a cell population expressing F4/80(+)/Gr-1(+)surface markers, which adoptively suppressed naïve T-cell proliferation in vitro in response to anti-CD3/CD28 MAb stimulation in a cell-contact dependent manner. Soluble antigens with altered glycans by treatment with sodium periodate significantly reduced the recruitment of F4/80(+)/Gr1(+)cells, concomitantly their suppressive activity was abrogated, indicating that glycans have a role in the early activation of these suppressor cells. Using C3H/HeJ and STAT6-KO mice, we found that expansion and suppressive activity of F4/80(+)Gr1(+)cells induced by T. crassiceps intact antigens was TLR4 and Th2-type cytokine independent. Together with previous studies on nematode and trematode parasites, our data support the hypothesis that glycans can be involved on a similar pathway in the immunoregulation by helminths.

Parasitic infections are one of the most important causes of morbidity and mortality in our planet and the immune responses triggered by these organisms are critical to determine their outcome. Dendritic cells are key elements for the development of immunity against parasites; they control the responses required to eliminate these pathogens while maintaining host homeostasis. However, there is evidence showing that parasites can influence and regulate dendritic cell function in order to promote a more permissive environment for their survival. In this review we will focus on the strategies protozoan and helminth parasites have developed to interfere with dendritic cell activities as well as in the possible mechanisms involved.

Sexual dimorphisms exist in the incidence and severity of many diseases, with females demonstrating relative protection from inflammatory conditions. The extent and mechanisms by which excessive leukocyte recruitment underlies these differences are not well established, and better understanding is essential for the development of targeted therapies. Here, we set out to compare the male and female inflammatory response in a murine zymosan-induced peritonitis model and to understand how leukocyte subsets are mobilized from storage pools in both sexes. This work shows that female C57BL/6 mice recruit fewer classical monocytes and neutrophils during zymosan-induced peritonitis. In addition, sex differences were evident in the circulation, as female mice showed reduced neutrophilia and monocytosis vs. male counterparts, despite having similar mobilization from BM stores. Importantly, we show that storage and trafficking of splenic leukocytes during acute inflammation are distinct between the sexes. Male mice have greater splenic stores of neutrophils and classical and nonclassical monocytes, despite similar spleen sizes, signifying another source of potential pathogenic leukocytes. This work demonstrates that males and females have distinct leukocyte-trafficking profiles in acute inflammation and suggests that the spleen, not the BM, plays a role in determining sex differences in the available pool of immune cells. Such dimorphisms demonstrate the importance of considering gender in assay development, drug design, and clinical trials.

Pathogens have developed strategies to modify Dendritic Cells (DCs) phenotypes and impair their functions in order to create a safer environment for their survival. DCs responses to helminths and their derivatives vary among different studies. Here we show that excretory/secretory products of the cestode Taenia crassiceps (TcES) do not induce the maturation of human DCs judged by a lack of increment in the expression of CD83, HLA-DR, CD80 and CD86 molecules but enhanced the production of IL-10 and positively modulated the expression of the C-type lectin receptor MGL and negatively modulated the expression of DC-SIGN. Additionally, these antigens were capable of down-modulating the inflammatory response induced by LPS in these cells by reducing the expression of the maturation markers and the production of the inflammatory cytokines IL-1β, TNF, IL-12 and IL-6. The effects of TcES upon the DCs responses to LPS were stronger if cells were exposed during their differentiation to the helminth antigens. All together, these findings suggest the ability of TcES to induce the differentiation of human DCs into a tolerogenic-like phenotype and to inhibit the effects of inflammatory stimuli.

Common helminth infections promote Th2-skewed immune responses in their hosts. We have studied the role of intact carbohydrate structures on Taenia crassiceps compounds in the induction of biased type 2 and anti-inflammatory immune responses on peptidestimulated T cells by using DO11.10 transgenic (OVA Tg) mice. While OVA Tg mice co-injected with OVA peptide [323][324][325][326][327][328][329][330][331][332][333][334][335][336][337][338][339]