4 research outputs found
Modulation of Specific and Allergy-Related Immune Responses by Helminths
Helminths are master regulators of host immune responses utilising complex mechanisms to dampen host protective Th2-type responses and favour long-term persistence. Such evasion mechanisms ensure mutual survival of both the parasite and the host. In this paper, we present recent findings on the cells that are targeted by helminths and the molecules and mechanisms that are induced during infection. We discuss the impact of these factors on the host response as well as their effect in preventing the development of aberrant allergic inflammation. We also examine recent findings on helminth-derived molecules that can be used as tools to pinpoint the underlying mechanisms of immune regulation or to determine new anti-inflammatory therapeutics
Brugia malayi Microfilariae Induce a Regulatory Monocyte/Macrophage Phenotype That Suppresses Innate and Adaptive Immune Responses
Background Monocytes and macrophages contribute to the dysfunction of immune
responses in human filariasis. During patent infection monocytes encounter
microfilariae in the blood, an event that occurs in asymptomatically infected
filariasis patients that are immunologically hyporeactive. Aim To determine
whether blood microfilariae directly act on blood monocytes and in vitro
generated macrophages to induce a regulatory phenotype that interferes with
innate and adaptive responses. Methodology and principal findings Monocytes
and in vitro generated macrophages from filaria non-endemic normal donors were
stimulated in vitro with Brugia malayi microfilarial (Mf) lysate. We could
show that monocytes stimulated with Mf lysate develop a defined regulatory
phenotype, characterised by expression of the immunoregulatory markers IL-10
and PD-L1. Significantly, this regulatory phenotype was recapitulated in
monocytes from Wuchereria bancrofti asymptomatically infected patients but not
patients with pathology or endemic normals. Monocytes from non-endemic donors
stimulated with Mf lysate directly inhibited CD4+ T cell proliferation and
cytokine production (IFN-γ, IL-13 and IL-10). IFN-γ responses were restored by
neutralising IL-10 or PD-1. Furthermore, macrophages stimulated with Mf lysate
expressed high levels of IL-10 and had suppressed phagocytic abilities.
Finally Mf lysate applied during the differentiation of macrophages in vitro
interfered with macrophage abilities to respond to subsequent LPS stimulation
in a selective manner. Conclusions and significance Conclusively, our study
demonstrates that Mf lysate stimulation of monocytes from healthy donors in
vitro induces a regulatory phenotype, characterized by expression of PD-L1 and
IL-10. This phenotype is directly reflected in monocytes from filarial
patients with asymptomatic infection but not patients with pathology or
endemic normals. We suggest that suppression of T cell functions typically
seen in lymphatic filariasis is caused by microfilaria-modulated monocytes in
an IL-10-dependent manner. Together with suppression of macrophage innate
responses, this may contribute to the overall down-regulation of immune
responses observed in asymptomatically infected patients
STUDYING WOMEN'S SUBSTANTIVE REPRESENTATION IN LEGISLATURES: WHEN REPRESENTATIVE ACTS, CONTEXTS AND WOMEN'S INTERESTS BECOME IMPORTANT
The lack of consensus regarding what the substantive representation of women means involves far reaching consequences for empirical research. This article illustrates some consequences of specific operationalisations of 'the substantive representation of women'. It shows that, in order to understand the substantive representation of women, as it is performed by multiple representatives, empirical research needs to encompass a broad range of representative acts and contexts. It also benefits from including a wide conception of women's interests and women's perspectives