Human Cellular Immune Response to the Saliva of Phlebotomus papatasi Is Mediated by IL-10-Producing CD8+ T Cells and Th1-Polarized CD4+ Lymphocytes

Abdeladhim, Maha; Ahmed, Mélika Ben; Marzouki, Soumaya; Hmida, Nedia; Boussoffara, Thouraya; Hamida, Nabil Belhaj; Salah, Afif Ben; Louzir, Hechmi

doi:10.1371/journal.pntd.0001345

Cited by 38 publications

(49 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Similarly to our results, a specific proliferative response to P . papatasi saliva was showed in 30% of a small group of exposed donors in a CL endemic area and no correlation was observed between these responses and proliferation to soluble Leishmania antigens [41]. However, absence of IFN-γ and IL-10 production by T CD8+ cells, in favor a Th2-type cellular response, was observed in this work.…”

Section: Discussionmentioning

confidence: 57%

“…It was shown that P . papatasi saliva was able to induce the activation of IL-10 producing T cells in naturally exposed individuals [41]. Although we did not detect any significant IL-10 production in response to SGE, we further analyzed proliferation and IFN-γ production to SGE in the presence of an anti-human IL-10 antibody, in order to determine whether the observed SGE-specific cellular responses are down-regulated.…”

Section: Resultsmentioning

confidence: 96%

“…papatasi saliva in PBMC from individuals naturally exposed to L . major infection, showed low proliferation, absence of IFN-γ production but significant IL-10 levels, which could favor establishment of infection [41]. …”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

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

Self Cite

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionmentioning

confidence: 57%

Section: Resultsmentioning

confidence: 96%

See 1 more Smart Citation

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

Self Cite

View full text Add to dashboard Cite

show abstract

“…In similar fashion, MDDCs from Iraq-based military personnel donors bitten by sand flies but not infected with Leishmania induced significantly less cellular proliferation compared with unexposed donors (Figure 5B). A recent report52 showed that CD4 + T cells from sand fly-exposed humans stimulated with SGS expressed high levels of IFN-γ. When CD8 + T cells from the same donors were stimulated with SGS, high amounts of IL-10 were produced.…”

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

View full text Add to dashboard Cite

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.

show abstract

“…In contrast, the natural immune response to mosquito bites does not afford protection against malaria, and experimental models of mosquito exposure do not demonstrate substantial protection against Plasmodium (Kebaier et al, 2010; Pollock et al, 2011). This may be attributed to several factors, including the quantity of saliva secreted into the host (Abdeladhim et al, 2011), the short duration of a mosquito bite (Kebaier et al, 2010), and/or the relative immunogenicity of specific proteins in the natural milieu of saliva compared with artificial hyper-immunization. In contrast, the A. gambiae SGE antisera, prepared in rabbits using Freund’s adjuvant, elicited robust and diverse responses to numerous proteins in saliva.…”

Section: Discussionmentioning

confidence: 99%

Immunization with AgTRIO, a Protein in Anopheles Saliva, Contributes to Protection against Plasmodium Infection in Mice

Dragovic

Agunbiade

Freudzon

et al. 2018

Cell Host & Microbe

View full text Add to dashboard Cite

SUMMARY Plasmodium infection begins with the bite of an anopheline mosquito, when sporozoites along with saliva are injected into a vertebrate host. The role of the host responses to mosquito saliva components in malaria remains unclear. We observed that antisera against Anopheles gambiae salivary glands partially protected mice from mosquito-borne Plasmodium infection. Specifically, antibodies to A. gambiae TRIO (AgTRIO), a mosquito salivary gland antigen, contributed to the protection. Mice administered AgTRIO antiserum showed lower Plasmodium liver burden and decreased parasitemia when exposed to infected mosquitoes. Active immunization with AgTRIO was also partially protective against Plasmodium berghei infection. A combination of AgTRIO antiserum and antibodies against Plasmodium circumsporozoite protein, a vaccine candidate, further decreased P. berghei infection. In humanized mice, AgTRIO antiserum afforded some protection against mosquito-transmitted Plasmodium falciparum. AgTRIO antiserum reduced the movement of sporozoites in the murine dermis. AgTRIO may serve as an arthropod-based target against Plasmodium to combat malaria.

show abstract

Human Cellular Immune Response to the Saliva of Phlebotomus papatasi Is Mediated by IL-10-Producing CD8+ T Cells and Th1-Polarized CD4+ Lymphocytes

Cited by 38 publications

References 35 publications

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

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

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

Immunization with AgTRIO, a Protein in Anopheles Saliva, Contributes to Protection against Plasmodium Infection in Mice

Contact Info

Product

Resources

About