18 research outputs found
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
Filarial Lymphedema Is Characterized by Antigen- Specific Th1 and Th17 Proinflammatory Responses and a Lack of Regulatory T Cells
Background: Lymphatic filariasis can be associated with development of serious pathology in the form of lymphedema,
hydrocele, and elephantiasis in a subset of infected patients.
Methods and Findings: To elucidate the role of CD4+ T cell subsets in the development of lymphatic pathology, we
examined specific sets of cytokines in individuals with filarial lymphedema in response to parasite antigen (BmA) and
compared them with responses from asymptomatic infected individuals. We also examined expression patterns of Toll-like
receptors (TLR1–10) and Nod-like receptors (Nod1, Nod2, and NALP3) in response to BmA. BmA induced significantly higher
production of Th1-type cytokines—IFN-c and TNF-a—in patients with lymphedema compared with asymptomatic
individuals. Notably, expression of the Th17 family of cytokines—IL-17A, IL-17F, IL-21, and IL-23—was also significantly
upregulated by BmA stimulation in lymphedema patients. In contrast, expression of Foxp3, GITR, TGFb, and CTLA-4, known
to be expressed by regulatory T cells, was significantly impaired in patients with lymphedema. BmA also induced
significantly higher expression of TLR2, 4, 7, and 9 as well Nod1 and 2 mRNA in patients with lymphedema compared with
asymptomatic controls.
Conclusion: Our findings implicate increased Th1/Th17 responses and decreased regulatory T cells as well as regulation of
Toll- and Nod-like receptors in pathogenesis of filarial lymphedema
Stage- and Gender-Specific Proteomic Analysis of Brugia malayi Excretory-Secretory Products
To succeed in infection, parasites must have ways to reach the host, penetrate its tissues and escape its defense systems. As they are not necessarily fatal, most helminth parasites remain viable within their host for many years, exerting a strong influence over the host immune function. Many of these functions are performed by products that are released from the parasite. We exploited the remarkable sensitivity of modern proteomics tools together with the availability of a sequenced genome to identify and compare the proteins released in vitro by adult males, adult females and the microfilariae of the filarial nematode Brugia malayi. This parasite is one of the etiological agents of lymphatic filariasis, a disease that poses continuing and significant threats to human health. The different forms of the parasite inhabit different compartments in the mammalian host. We found that the set of proteins released by each form is unique; they must reflect particular developmental processes and different strategies for evasion of host responses. The identification of these proteins will allow us to illuminate the biology of secretory processes in this organism and to establish a path for developing an understanding of how these parasite proteins function in immune evasion events
Dectin-1: a role in antifungal defense and consequences of genetic polymorphisms in humans
The clinical relevance of fungal infections has increased dramatically in recent decades as a consequence of the rise of immunocompromised populations, and efforts to understand the underlying mechanisms of protective immunity have attracted renewed interest. Here we review Dectin-1, a pattern recognition receptor involved in antifungal immunity, and discuss recent discoveries of polymorphisms in the gene encoding this receptor which result in human disease
The role of packaging for consumer products: understanding the move towards ‘plain’ tobacco packaging
The Australian Government intends to introduce plain tobacco packaging in 2012. We consider whether such a move appears justified by examining the wider marketing literature in order to understand the role that packaging has for consumer goods. Packaging is often called the fifth ‘p’ of the marketing mix. It is an effective marketing medium for all consumer products and helps build consumer relationships through possession and usage. Common packaging strategies to promote the product, distinguish products from competitors, communicate brand values and target specific consumer groups include innovative, special edition, value and green packaging. These strategies, combined with the visual and structural aspects of packaging design, such as colour, size and shape, influence consumer perceptions and purchase and usage behaviour. This gives packaging an important role at point-of-purchase and also post-purchase. Packaging also has a close relationship with the product, influencing perceived product attributes, and is a key representative of the brand. We conclude that plain tobacco packaging appears justified, based on the importance of packaging as a promotional tool, and will fundamentally restrict the opportunity for tobacco companies to influence consumers through package design