PpSP32, the Phlebotomus papatasi immunodominant salivary protein, exerts immunomodulatory effects on human monocytes, macrophages, and lymphocytes
Abstract Background The saliva of sand flies, vectors of Leishmania parasites, contains several components that exert pharmacological activity facilitating the acquisition of blood by the insect and contributing to the establishment of infection. Previously, we demonstrated that PpSP32 is the immuno...
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| Format: | Article |
| Language: | English |
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BMC
2023-01-01
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| Series: | Parasites & Vectors |
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| Online Access: | https://doi.org/10.1186/s13071-022-05627-7 |
| _version_ | 1828069751787618304 |
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| author | Cyrine Souissi Soumaya Marzouki Ines Elbini-Dhouib Jed Jebali Fabiano Oliveira Jesus G. Valenzuela Najet Srairi-Abid Shaden Kamhawi Melika Ben Ahmed |
| author_facet | Cyrine Souissi Soumaya Marzouki Ines Elbini-Dhouib Jed Jebali Fabiano Oliveira Jesus G. Valenzuela Najet Srairi-Abid Shaden Kamhawi Melika Ben Ahmed |
| author_sort | Cyrine Souissi |
| collection | DOAJ |
| description | Abstract Background The saliva of sand flies, vectors of Leishmania parasites, contains several components that exert pharmacological activity facilitating the acquisition of blood by the insect and contributing to the establishment of infection. Previously, we demonstrated that PpSP32 is the immunodominant salivary antigen in humans exposed to Phlebotomus papatasi bites and validated its usefulness as a predictive biomarker of disease. PpSP32, whose functions are little known to date, is an intriguing protein due to its involvement in the etiopathogenesis of pemphigus, an auto-immune disease. Herein, we aimed to better decipher its role through the screening of several immunomodulatory activity either on lymphocytes or on monocytes/macrophages. Methods Peripheral mononuclear cells from healthy volunteers were stimulated with anti-CD3/anti-CD28 antibodies, phytohemagglutinin, phorbol 12-myristate 13-acetate/ionomycin, or lipopolysaccharide in the presence of increasing doses of PpSP32. Cell proliferation was measured after the addition of tritiated thymidine. Monocyte activation was tested by analyzing the expression of CD86 and HLA-DR molecules by flow cytometry. Cytokine production was analyzed in culture supernatants by ELISA. THP-1-derived macrophages were stimulated with LPS in the presence of increasing doses of PpSP32, and cytokine production was analyzed in culture supernatants by ELISA and multiplex technique. The effect of PpSP32 on NF-kB signaling was tested by Western blot. The anti-inflammatory activity of PpSP32 was assessed in vivo in an experimental inflammatory model of carrageenan-induced paw edema in rats. Results Our data showed that PpSP32 down-modulated the expression of activation markers in LPS-stimulated monocytes and THP1-derived macrophages. This protein negatively modulated the secretion of Th1 and Th2 cytokines by human lymphocytes as well as pro-inflammatory cytokines by monocytes, and THP1-derived macrophages. PpSP32 treatment led to a dose-dependent reduction of IκB phosphorylation. When PpSP32 was injected into the paw of carrageenan-injected rats, edema was significantly reduced. Conclusions Our data indicates that PpSP32 induces a potent immunomodulatory effect on monocytes and THP-1-derived macrophages. This inhibition could be mediated, among others, by the modulation of the NF-kB signaling pathway. The anti-inflammatory activity of PpSP32 was confirmed in vivo in the carrageenan-induced paw edema model in rats. Graphical Abstract |
| first_indexed | 2024-04-11T00:24:09Z |
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| id | doaj.art-8cf4f36db80648c89b5e03a6dd50d4c2 |
| institution | Directory Open Access Journal |
| issn | 1756-3305 |
| language | English |
| last_indexed | 2024-04-11T00:24:09Z |
| publishDate | 2023-01-01 |
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| series | Parasites & Vectors |
| spelling | doaj.art-8cf4f36db80648c89b5e03a6dd50d4c22023-01-08T12:06:01ZengBMCParasites & Vectors1756-33052023-01-0116111210.1186/s13071-022-05627-7PpSP32, the Phlebotomus papatasi immunodominant salivary protein, exerts immunomodulatory effects on human monocytes, macrophages, and lymphocytesCyrine Souissi0Soumaya Marzouki1Ines Elbini-Dhouib2Jed Jebali3Fabiano Oliveira4Jesus G. Valenzuela5Najet Srairi-Abid6Shaden Kamhawi7Melika Ben Ahmed8Laboratory of Transmission, Control and Immunobiology of Infections (LTCII), LR11IPT02, Pasteur Institute de TunisLaboratory of Transmission, Control and Immunobiology of Infections (LTCII), LR11IPT02, Pasteur Institute de TunisLaboratory of Biomolecules, Venoms and Theranostic Applications, LR20IPT01, Pasteur Institute of Tunis, University of Tunis El ManarLaboratory of Biomolecules, Venoms and Theranostic Applications, LR20IPT01, Pasteur Institute of Tunis, University of Tunis El ManarVector Molecular Biology Section, Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institute of HealthVector Molecular Biology Section, Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institute of HealthLaboratory of Biomolecules, Venoms and Theranostic Applications, LR20IPT01, Pasteur Institute of Tunis, University of Tunis El ManarVector Molecular Biology Section, Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institute of HealthLaboratory of Transmission, Control and Immunobiology of Infections (LTCII), LR11IPT02, Pasteur Institute de TunisAbstract Background The saliva of sand flies, vectors of Leishmania parasites, contains several components that exert pharmacological activity facilitating the acquisition of blood by the insect and contributing to the establishment of infection. Previously, we demonstrated that PpSP32 is the immunodominant salivary antigen in humans exposed to Phlebotomus papatasi bites and validated its usefulness as a predictive biomarker of disease. PpSP32, whose functions are little known to date, is an intriguing protein due to its involvement in the etiopathogenesis of pemphigus, an auto-immune disease. Herein, we aimed to better decipher its role through the screening of several immunomodulatory activity either on lymphocytes or on monocytes/macrophages. Methods Peripheral mononuclear cells from healthy volunteers were stimulated with anti-CD3/anti-CD28 antibodies, phytohemagglutinin, phorbol 12-myristate 13-acetate/ionomycin, or lipopolysaccharide in the presence of increasing doses of PpSP32. Cell proliferation was measured after the addition of tritiated thymidine. Monocyte activation was tested by analyzing the expression of CD86 and HLA-DR molecules by flow cytometry. Cytokine production was analyzed in culture supernatants by ELISA. THP-1-derived macrophages were stimulated with LPS in the presence of increasing doses of PpSP32, and cytokine production was analyzed in culture supernatants by ELISA and multiplex technique. The effect of PpSP32 on NF-kB signaling was tested by Western blot. The anti-inflammatory activity of PpSP32 was assessed in vivo in an experimental inflammatory model of carrageenan-induced paw edema in rats. Results Our data showed that PpSP32 down-modulated the expression of activation markers in LPS-stimulated monocytes and THP1-derived macrophages. This protein negatively modulated the secretion of Th1 and Th2 cytokines by human lymphocytes as well as pro-inflammatory cytokines by monocytes, and THP1-derived macrophages. PpSP32 treatment led to a dose-dependent reduction of IκB phosphorylation. When PpSP32 was injected into the paw of carrageenan-injected rats, edema was significantly reduced. Conclusions Our data indicates that PpSP32 induces a potent immunomodulatory effect on monocytes and THP-1-derived macrophages. This inhibition could be mediated, among others, by the modulation of the NF-kB signaling pathway. The anti-inflammatory activity of PpSP32 was confirmed in vivo in the carrageenan-induced paw edema model in rats. Graphical Abstracthttps://doi.org/10.1186/s13071-022-05627-7Phlebotomus papatasiLeishmaniasisSalivaPpSP32Immunomodulatory effects |
| spellingShingle | Cyrine Souissi Soumaya Marzouki Ines Elbini-Dhouib Jed Jebali Fabiano Oliveira Jesus G. Valenzuela Najet Srairi-Abid Shaden Kamhawi Melika Ben Ahmed PpSP32, the Phlebotomus papatasi immunodominant salivary protein, exerts immunomodulatory effects on human monocytes, macrophages, and lymphocytes Parasites & Vectors Phlebotomus papatasi Leishmaniasis Saliva PpSP32 Immunomodulatory effects |
| title | PpSP32, the Phlebotomus papatasi immunodominant salivary protein, exerts immunomodulatory effects on human monocytes, macrophages, and lymphocytes |
| title_full | PpSP32, the Phlebotomus papatasi immunodominant salivary protein, exerts immunomodulatory effects on human monocytes, macrophages, and lymphocytes |
| title_fullStr | PpSP32, the Phlebotomus papatasi immunodominant salivary protein, exerts immunomodulatory effects on human monocytes, macrophages, and lymphocytes |
| title_full_unstemmed | PpSP32, the Phlebotomus papatasi immunodominant salivary protein, exerts immunomodulatory effects on human monocytes, macrophages, and lymphocytes |
| title_short | PpSP32, the Phlebotomus papatasi immunodominant salivary protein, exerts immunomodulatory effects on human monocytes, macrophages, and lymphocytes |
| title_sort | ppsp32 the phlebotomus papatasi immunodominant salivary protein exerts immunomodulatory effects on human monocytes macrophages and lymphocytes |
| topic | Phlebotomus papatasi Leishmaniasis Saliva PpSP32 Immunomodulatory effects |
| url | https://doi.org/10.1186/s13071-022-05627-7 |
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