American Tegumentary Leishmaniasis: Cytokines and Nitric Oxide in Active Disease and After Clinical Cure, With or Without Chemotherapy

Souza, M. A.; Castro, Maria Carolina Accioly Brelaz de; Oliveira, Andresa Pereira de; Almeida, André; Reis, Luiza Campos; Silva, C. J.; Brito, Maria Edileuza Felinto de; Pereira, Valéria Rêgo Alves

doi:10.1111/j.1365-3083.2012.02717.x

Cited by 23 publications

(18 citation statements)

References 31 publications

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“…Consistent with this, it has been reported that the injection of anti-TNF-α into mice worsened the Leishmania infection [51]. The phenomena described above could perhaps underlie the protective response that normally keeps the Leishmania parasites in check in most infected human beings [52], [53].…”

Section: Discussionsupporting

confidence: 69%

Extracellular Vesicles from Leishmania-Infected Macrophages Confer an Anti-infection Cytokine-Production Profile to Naïve Macrophages

et al. 2014

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BackgroundExtracellular vesicles (EVs) are structures with phospholipid bilayer membranes and 100–1000 nm diameters. These vesicles are released from cells upon activation of surface receptors and/or apoptosis. The production of EVs by dendritic cells, mast cells, macrophages, and B and T lymphocytes has been extensively reported in the literature. EVs may express MHC class II and other membrane surface molecules and carry antigens. The aim of this study was to investigate the role of EVs from Leishmania-infected macrophages as immune modulatory particles.Methodology/Principal FindingsIn this work it was shown that BALB/c mouse bone marrow-derived macrophages, either infected in vitro with Leishmania amazonensis or left uninfected, release comparable amounts of 50–300 nm-diameter extracellular vesicles (EVs). The EVs were characterized by flow cytometry and electron microscopy. The incubation of naïve macrophages with these EVs for 48 hours led to a statistically significant increase in the production of the cytokines IL-12, IL-1β, and TNF-α.Conclusions/SignificanceEVs derived from macrophages infected with L. amazonensis induce other macrophages, which in vivo could be bystander cells, to produce the proinflammatory cytokines IL-12, IL-1β and TNF-α. This could contribute both to modulate the immune system in favor of a Th1 immune response and to the elimination of the Leishmania, leading, therefore, to the control the infection.

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Section: Discussionsupporting

confidence: 69%

Extracellular Vesicles from Leishmania-Infected Macrophages Confer an Anti-infection Cytokine-Production Profile to Naïve Macrophages

et al. 2014

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“…Conversely, we found an increase in IL-17 production in patients infected with L. braziliensis , and there was a direct correlation between the magnitude of the cellular infiltrate and IL-17 [16]. Similarly, IL-17 levels were elevated in L. braziliensis infected patients with disease, but not patients who have resolved their infections [68]. Finally, an association with increased IL-17 and neutrophils has been observed in mucosal patients [17].…”

Section: Discussionmentioning

confidence: 48%

IL-17 Mediates Immunopathology in the Absence of IL-10 Following Leishmania major Infection

et al. 2013

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Leishmaniasis, resulting from infection with the protozoan parasite Leishmania, consists of a wide spectrum of clinical manifestations, from healing cutaneous lesions to fatal visceral infections. A particularly severe form of cutaneous leishmaniasis, termed mucosal leishmaniasis, exhibits decreased IL-10 levels and an exaggerated inflammatory response that perpetuates the disease. Using a mouse model of leishmaniasis, we investigated what cytokines contribute to increased pathology when IL-10-mediated regulation is absent. Leishmania major infected C57BL/6 mice lacking IL-10 regulation developed larger lesions than controls, but fewer parasites. Both IFN-γ and IL-17 levels were substantially elevated in mice lacking the capacity to respond to IL-10. IFN-γ promoted an increased infiltration of monocytes, while IL-17 contributed to an increase in neutrophils. Surprisingly, however, we found that IFN-γ did not contribute to increased pathology, but instead regulated the IL-17 response. Thus, blocking IFN-γ led to a significant increase in IL-17, neutrophils and disease. Similarly, the production of IL-17 by cells from leishmaniasis patients was also regulated by IL-10 and IFN-γ. Additional studies found that the IL-1 receptor was required for both the IL-17 response and increased pathology. Therefore, we propose that regulating IL-17, possibly by downregulating IL-1β, may be a useful approach for controlling immunopathology in leishmaniasis.

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“…Bone marrow-derived dendritic cells pre-exposed to salivary gland extracts from the South American Leishmania sand fly vector L. longipalpis exhibited diminished IL-17 expression when secondarily challenged to inflammation 48. Moreover, peripheral blood mononuclear cells from human donors who self-healed from cutaneous disease expressed less IL-17 compared with individuals presenting with active disease after in vitro rechallenge with soluble Leishmania antigens 55. IL-8 and IP-10 (CXCL10) are potent chemotactic agents responsible for recruitment of neutrophils, monocytes, and other immune cell types and have been shown to be responsible for the abrogation of the visceral forms of leishmaniasis 56.…”

Section: Discussionmentioning

confidence: 99%

Profiling of Human Acquired Immunity Against the Salivary Proteins of Phlebotomus papatasi Reveals Clusters of Differential Immunoreactivity

Geraci¹,

Mukbel²,

Kemp³

et al. 2014

The American Society of Tropical Medicine and Hygiene

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Phlebotomus papatasi sand flies are among the primary vectors of Leishmania major parasites from Morocco to the Indian subcontinent and from southern Europe to central and eastern Africa. Antibody-based immunity to sand fly salivary gland proteins in human populations remains a complex contextual problem that is not yet fully understood. We profiled the immunoreactivities of plasma antibodies to sand fly salivary gland sonicates (SGSs) from 229 human blood donors residing in different regions of sand fly endemicity throughout Jordan and Egypt as well as 69 US military personnel, who were differentially exposed to P. papatasi bites and L. major infections in Iraq. Compared with plasma from control region donors, antibodies were significantly immunoreactive to five salivary proteins (12, 26, 30, 38, and 44 kDa) among Jordanian and Egyptian donors, with immunoglobulin G4 being the dominant anti-SGS isotype. US personnel were significantly immunoreactive to only two salivary proteins (38 and 14 kDa). Using k-means clustering, donors were segregated into four clusters distinguished by unique immunoreactivity profiles to varying combinations of the significantly immunogenic salivary proteins. SGS-induced cellular proliferation was diminished among donors residing in sand fly-endemic regions. These data provide a clearer picture of human immune responses to sand fly vector salivary constituents.

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American Tegumentary Leishmaniasis: Cytokines and Nitric Oxide in Active Disease and After Clinical Cure, With or Without Chemotherapy

Cited by 23 publications

References 31 publications

Extracellular Vesicles from Leishmania-Infected Macrophages Confer an Anti-infection Cytokine-Production Profile to Naïve Macrophages

Extracellular Vesicles from Leishmania-Infected Macrophages Confer an Anti-infection Cytokine-Production Profile to Naïve Macrophages

IL-17 Mediates Immunopathology in the Absence of IL-10 Following Leishmania major Infection

Profiling of Human Acquired Immunity Against the Salivary Proteins of Phlebotomus papatasi Reveals Clusters of Differential Immunoreactivity

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