Glycoinositolphospholipids from Trypanosomatids Subvert Nitric Oxide Production in Rhodnius prolixus Salivary Glands

Gazos-Lopes, Felipe; Mesquita, Rafael D.; Silva-Cardoso, Lívia; Senna, Raquel; Silveira, Alan Barbosa da; Jablonka, Willy; Cudischevitch, Cecília Oliveira; Carneiro, A.; Machado, Ednildo A.; Lima, Luize Gonçalves; Monteiro, Robson Q.; Nussenzveig, Roberto; Folly, Evelize; Romeiro, Alexandre; Vanbeselaere, Jorick; Mendonça-Previato, Lúcia; Previato, José O.; Valenzuela, Jesús G.; Ribeiro, José M. C.; Atella, Geórgia C.; Silva-Neto, Mário A.C.

doi:10.1371/journal.pone.0047285

Cited by 21 publications

(19 citation statements)

References 62 publications

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“…The ceramide portion was able to induce apoptosis in activated macrophages (54) and to suppress T cell activation in mammal cells (55). Additionally, GIPL from T. cruzi and T. rangeli decreased the production of nitric oxide in the insect's salivary glands, being this an important initial step for parasite survival (56).…”

Section: Discussionmentioning

confidence: 99%

Thiol efflux mediated by an ABCC-like transporter participates forTrypanosoma cruziadaptation to environmental and chemotherapeutic stresses

Costa

et al. 2020

Preprint

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The protozoan Trypanosoma cruzi is the etiologic agent for Chagas disease, which affects 6-7 million people worldwide. The parasite presents high biological diversity, reflecting on the inefficiency of benznidazole in chronic or older patients. ABC superfamily proteins contain active transporters involved in the xenobiotic and endobiotic efflux and overexpressed in MDR cells. An ABCC-like transport was identified in the T. cruzi Y strain, being able to extrude thiol-conjugated compounds. As non-protein thiols represent prime line of defense towards reactive species, ABCC-like activity could participate in the regulation of mediators implicated in responses to cellular stress arising from a variety of stimuli, as environmental or chemotherapeutic. This study shows that T. cruzi ABCC-like protein transports GSH, GSSG and ceramides, all implicated in cellular stress. Hemin, representative from the hematophagous feeding of the vector, was transported as well, suggesting a role for ABCC as a metal-thiol transporter. In addition, all strains evaluated showed ABCC-like activity, while no ABCB1-like activity was detected. Also, results suggest that ABCC-like does not associate to natural resistance to benznidazole, considering that the sensitive strains CL Brener and Berenice showed higher ABCC-like activity than the resistant strains Y and Colombiana. Instead, ABCC-like efflux increased after continuous exposure of Y strain to benznidazole. Moreover, ABCC does not perform direct efflux of drug and its participation in the machinery of protection against stress depends on the efflux of metabolites in conjugation to or in cotransport with thiol.

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Section: Discussionmentioning

confidence: 99%

Thiol efflux mediated by an ABCC-like transporter participates forTrypanosoma cruziadaptation to environmental and chemotherapeutic stresses

Costa

et al. 2020

Preprint

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“…Within the emerging focus, where infecting bites are probably fewer than in the old focus, we showed a significant IFN-γ production only in naïve individuals, suggesting that the anti-saliva cellular immune responses vary depending on whether the host is exposed to saliva in the presence or absence of parasites. Host-parasite interactions within the insect vector before transmission could alter the vector salivary protein profile that may consequently influence the immune response of the human host [52]. A role of the parasite in diminishing host antibody production against a salivary protein was suggested in a study showing a decrease in the immunogenicity of this protein in infected donors compared to donors exposed to sand fly bites but not infected [53].…”

Section: Discussionmentioning

confidence: 99%

Human cellular and humoral immune responses to Phlebotomus papatasi salivary gland antigens in endemic areas differing in prevalence of Leishmania major infection

et al. 2017

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BackgroundSand fly saliva compounds are able to elicit specific immune responses that have a significant role in Leishmania parasite establishment and disease outcome. Characterizing anti-saliva immune responses in individuals living in well defined leishmaniasis endemic areas would provide valuable insights regarding their effect on parasite transmission and establishment in humans.Methodology/Principal findingsWe explored the cellular and humoral immune responses to Phlebotomus (P.) papatasi salivary gland extracts (SGE) in individuals living in cutaneous leishmaniasis (CL) old or emerging foci (OF, EF). OF was characterized by a higher infection prevalence as assessed by higher proportions of leishmanin skin test (LST) positive individuals compared to EF. Subjects were further subdivided into healed, asymptomatic or naïve groups. We showed anti-SGE proliferation in less than 30% of the individuals, regardless of the immune status, in both foci. IFN-γ production was higher in OF and only observed in immune individuals from OF and naïve subjects from EF. Although IL-10 was not detected, addition of anti-human IL-10 antibodies revealed an increase in proliferation and IFN-γ production only in individuals from OF. The percentage of seropositive individuals was similar in immune and naïves groups but was significantly higher in OF. No correlation was observed between anti-saliva immune responses and LST response. High anti-SGE-IgG responses were associated with an increased risk of developing ZCL. No differences were observed for anti-SGE humoral or cellular responses among naïve individuals who converted or not their LST response or developed or not ZCL after the transmission season.Conclusions/SignificanceThese data suggest that individuals living in an old focus characterized by a frequent exposure to sand fly bites and a high prevalence of infection, develop higher anti-saliva IgG responses and IFN-γ levels and a skew towards a Th2-type cellular response, probably in favor of parasite establishment, compared to those living in an emerging focus.

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“…In agreement with previous observations of both the natural infection of the vector Phthia picta and the experimental infection of O. fasciatus with P. serpens , the parasite survives the invasion of the hemocoel and reaches the salivary gland [4], [25], a condition common to the life cycle of parasites that develop in the hemolymph within their respective vector, such as Plasmodium species and T. rangeli [26], [27]. This mode of infection is widely used for studying the interaction of trypanosomatids that invade the hemocoel of their insect hosts, especially in the model of interaction between T. rangeli with R. prolixus [28], [29].…”

Section: Discussionmentioning

confidence: 99%

The Immune Response of Hemocytes of the Insect Oncopeltus fasciatus against the Flagellate Phytomonas serpens

et al. 2013

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The genus Phytomonas includes parasites that are etiological agents of important plant diseases, especially in Central and South America. These parasites are transmitted to plants via the bite of an infected phytophagous hemipteran. Despite the economic impact of these parasites, many basic questions regarding the genus Phytomonas remain unanswered, such as the mechanism by which the parasites cope with the immune response of the insect vector. In this report, using a model of systemic infection, we describe the function of Oncopeltus fasciatus hemocytes in the immune response towards the tomato parasite Phytomonas serpens. Hemocytes respond to infection by trapping parasites in nodular structures and phagocytizing the parasites. In electron microscopy of hemocytes, parasites were located inside vacuoles, which appear fused with lysosomes. The parasites reached the O. fasciatus salivary glands at least six hours post-infection. After 72 hours post-infection, many parasites were attached to the salivary gland outer surface. Thus, the cellular responses did not kill all the parasites.

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Glycoinositolphospholipids from Trypanosomatids Subvert Nitric Oxide Production in Rhodnius prolixus Salivary Glands

Cited by 21 publications

References 62 publications

Thiol efflux mediated by an ABCC-like transporter participates forTrypanosoma cruziadaptation to environmental and chemotherapeutic stresses

Thiol efflux mediated by an ABCC-like transporter participates forTrypanosoma cruziadaptation to environmental and chemotherapeutic stresses

Human cellular and humoral immune responses to Phlebotomus papatasi salivary gland antigens in endemic areas differing in prevalence of Leishmania major infection

The Immune Response of Hemocytes of the Insect Oncopeltus fasciatus against the Flagellate Phytomonas serpens

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