{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,6]],"date-time":"2025-11-06T12:09:42Z","timestamp":1762430982102},"reference-count":56,"publisher":"Public Library of Science (PLoS)","issue":"4","license":[{"start":{"date-parts":[[2015,4,7]],"date-time":"2015-04-07T00:00:00Z","timestamp":1428364800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/publicdomain\/zero\/1.0\/"}],"content-domain":{"domain":["www.plosntds.org"],"crossmark-restriction":false},"short-container-title":["PLoS Negl Trop Dis"],"DOI":"10.1371\/journal.pntd.0003600","type":"journal-article","created":{"date-parts":[[2015,4,7]],"date-time":"2015-04-07T18:05:13Z","timestamp":1428429913000},"page":"e0003600","update-policy":"http:\/\/dx.doi.org\/10.1371\/journal.pntd.corrections_policy","source":"Crossref","is-referenced-by-count":19,"title":["Nucleosides Present on Phlebotomine Saliva Induce Immunossuppression and Promote the Infection Establishment"],"prefix":"10.1371","volume":"9","author":[{"given":"Vanessa","family":"Carregaro","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jos\u00e9 M.","family":"Ribeiro","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jesus G.","family":"Valenzuela","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Djalma L.","family":"Souza-J\u00fanior","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Diego L.","family":"Costa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carlo J. F.","family":"Oliveira","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"La\u00eds A.","family":"Sacramento","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manuela S. L.","family":"Nascimento","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cristiane M.","family":"Milanezi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fernando Q.","family":"Cunha","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jo\u00e3o S.","family":"Silva","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2015,4,7]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1146\/annurev.en.32.010187.002335","article-title":"Role of saliva in blood-feeding by arthropods","volume":"32","author":"JM Ribeiro","year":"1987","journal-title":"Annu Rev Entomol"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"1306","DOI":"10.1126\/science.3344436","article-title":"Salivary gland lysates from the sand fly Lutzomyia longipalpis enhance Leishmania infectivity","volume":"239","author":"RG Titus","year":"1988","journal-title":"Science"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"1941","DOI":"10.1084\/jem.188.10.1941","article-title":"Development of a natural model of cutaneous leishmaniasis: powerful effects of vector saliva and saliva preexposure on the long-term outcome of Leishmania major infection in the mouse ear dermis","volume":"188","author":"Y Belkaid","year":"1998","journal-title":"J Exp Med"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1084\/jem.173.1.49","article-title":"A mouse model of Leishmania braziliensis braziliensis infection produced by coinjection with sand fly saliva","volume":"173","author":"J Samuelson","year":"1991","journal-title":"J Exp Med"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"97","DOI":"10.2307\/3284537","article-title":"Histologic characterization of experimental cutaneous leishmaniasis in mice infected with Leishmania braziliensis in the presence or absence of sand fly vector salivary gland lysate","volume":"84","author":"KB Donnelly","year":"1998","journal-title":"J Parasitol"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1146\/annurev.ento.48.060402.102812","article-title":"Role of arthropod saliva in blood feeding: sialome and post-sialome perspectives","volume":"48","author":"JM Ribeiro","year":"2003","journal-title":"Annu Rev Entomol"},{"key":"ref7","first-page":"157","article-title":"Intracellular destruction of Leishmania tropica by macrophages activated with macrophage activating factor\/interferon","volume":"55","author":"RG Titus","year":"1984","journal-title":"Clin Exp Immunol"},{"key":"ref8","first-page":"437","article-title":"Interactions between Leishmania major and macrophages","volume":"60","author":"RG Titus","year":"1994","journal-title":"Immunol Ser"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1006\/expr.1998.4272","article-title":"Salivary gland lysate from the sand fly Lutzomyia longipalpis suppresses the immune response of mice to sheep red blood cells in vivo and concanavalin A in vitro","volume":"89","author":"RG Titus","year":"1998","journal-title":"Exp Parasitol"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1111\/j.1365-3024.2006.00807.x","article-title":"The immunomodulatory factors of arthropod saliva and the potential for these factors to serve as vaccine targets to prevent pathogen transmission","volume":"28","author":"RG Titus","year":"2006","journal-title":"Parasite Immunol"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"1077","DOI":"10.1084\/jem.180.3.1077","article-title":"Saliva of the Lyme disease vector, Ixodes dammini, blocks cell activation by a nonprostaglandin E2-dependent mechanism","volume":"180","author":"S Urioste","year":"1994","journal-title":"J Exp Med"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1084\/jem.194.3.331","article-title":"Toward a defined anti-Leishmania vaccine targeting vector antigens: characterization of a protective salivary protein","volume":"194","author":"JG Valenzuela","year":"2001","journal-title":"J Exp Med"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"1534","DOI":"10.1128\/IAI.66.4.1534-1537.1998","article-title":"Phlebotomus papatasi saliva inhibits protein phosphatase activity and nitric oxide production by murine macrophages","volume":"66","author":"J Waitumbi","year":"1998","journal-title":"Infect Immun"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"5442","DOI":"10.1128\/IAI.64.12.5442-5445.1996","article-title":"Effects of sand fly vector saliva on development of cutaneous lesions and the immune response to Leishmania braziliensis in BALB\/c mice","volume":"64","author":"HC Lima","year":"1996","journal-title":"Infect Immun"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"5571","DOI":"10.4049\/jimmunol.161.10.5571","article-title":"Phlebotomus papatasi sand fly salivary gland lysate down-regulates a Th1, but up-regulates a Th2, response in mice infected with Leishmania major","volume":"161","author":"ML Mbow","year":"1998","journal-title":"J Immunol"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1111\/j.0105-2896.2004.00198.x","article-title":"The development of effector and memory T cells in cutaneous leishmaniasis: the implications for vaccine development","volume":"201","author":"P Scott","year":"2004","journal-title":"Immunol Rev"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1111\/j.0105-2896.2004.00185.x","article-title":"Re-examination of the immunosuppressive mechanisms mediating non-cure of Leishmania infection in mice","volume":"201","author":"D Sacks","year":"2004","journal-title":"Immunol Rev"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1046\/j.1365-3024.1999.00211.x","article-title":"Indomethacin treatment slows disease progression and enhances a Th1 response in susceptible BALB\/c mice infected with Leishmania major","volume":"21","author":"LA De Freitas","year":"1999","journal-title":"Parasite Immunol"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1189\/jlb.1107797","article-title":"Phlebotomine salivas inhibit immune inflammation-induced neutrophil migration via an autocrine DC-derived PGE2\/IL-10 sequential pathway","volume":"84","author":"V Carregaro","year":"2008","journal-title":"J Leukoc Biol"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"4347","DOI":"10.4049\/jimmunol.1003404","article-title":"Nucleosides from Phlebotomus papatasi salivary gland ameliorate murine collagen-induced arthritis by impairing dendritic cell functions","volume":"187","author":"V Carregaro","year":"2011","journal-title":"J Immunol"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"1402","DOI":"10.1016\/j.micinf.2004.10.004","article-title":"Dendritic cells in Leishmania infection","volume":"6","author":"O Brandonisio","year":"2004","journal-title":"Microbes Infect"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"1914","DOI":"10.1172\/JCI114654","article-title":"Modulation of in vitro monocyte cytokine responses to Leishmania donovani. Interferon-gamma prevents parasite-induced inhibition of interleukin 1 production and primes monocytes to respond to Leishmania by producing both tumor necrosis factor-alpha and interleukin 1","volume":"85","author":"NE Reiner","year":"1990","journal-title":"J Clin Invest"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"418","DOI":"10.1093\/infdis\/167.2.418","article-title":"Parasitism of epidermal Langerhans cells in experimental cutaneous leishmaniasis with Leishmania major","volume":"167","author":"C Blank","year":"1993","journal-title":"J Infect Dis"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"1797","DOI":"10.1084\/jem.177.6.1797","article-title":"Resolution of cutaneous leishmaniasis: interleukin 12 initiates a protective T helper type 1 immune response","volume":"177","author":"JP Sypek","year":"1993","journal-title":"J Exp Med"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"5320","DOI":"10.4049\/jimmunol.154.10.5320","article-title":"IL-12 is required for natural killer cell activation and subsequent T helper 1 cell development in experimental leishmaniasis","volume":"154","author":"T Scharton-Kersten","year":"1995","journal-title":"J Immunol"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"3442","DOI":"10.1073\/pnas.90.8.3442","article-title":"Transforming growth factor beta as a virulence mechanism for Leishmania braziliensis","volume":"90","author":"A Barral","year":"1993","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"6704","DOI":"10.1073\/pnas.97.12.6704","article-title":"Delayed-type hypersensitivity to Phlebotomus papatasi sand fly bite: An adaptive response induced by the fly?","volume":"97","author":"Y Belkaid","year":"2000","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"1822","DOI":"10.1182\/blood-2008-02-136325","article-title":"Adenosine receptors in regulation of dendritic cell differentiation and function","volume":"112","author":"SV Novitskiy","year":"2008","journal-title":"Blood"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"e965","DOI":"10.1371\/journal.pntd.0000965","article-title":"BALB\/c mice infected with antimony treatment refractory isolate of Leishmania braziliensis present severe lesions due to IL-4 production","volume":"5","author":"DL Costa","year":"2011","journal-title":"PLoS Negl Trop Dis"},{"key":"ref30","doi-asserted-by":"crossref","first-page":"1551","DOI":"10.1242\/jeb.202.11.1551","article-title":"Salivary glands of the sand fly Phlebotomus papatasi contain pharmacologically active amounts of adenosine and 5&apos;-AMP","volume":"202","author":"JM Ribeiro","year":"1999","journal-title":"J Exp Biol"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1186\/1471-2180-13-102","article-title":"Dual effect of Lutzomyia longipalpis saliva on Leishmania braziliensis infection is mediated by distinct saliva-induced cellular recruitment into BALB\/c mice ear","volume":"13","author":"V Carregaro","year":"2013","journal-title":"BMC Microbiol"},{"key":"ref32","doi-asserted-by":"crossref","first-page":"1884","DOI":"10.4049\/jimmunol.179.3.1884","article-title":"Adenosine deamination sustains dendritic cell activation in inflammation","volume":"179","author":"MD Desrosiers","year":"2007","journal-title":"J Immunol"},{"key":"ref33","doi-asserted-by":"crossref","first-page":"610","DOI":"10.1038\/nri2132","article-title":"Tolerogenic dendritic cells and the quest for transplant tolerance","volume":"7","author":"AE Morelli","year":"2007","journal-title":"Nat Rev Immunol"},{"key":"ref34","doi-asserted-by":"crossref","first-page":"1765","DOI":"10.4049\/jimmunol.0902133","article-title":"Tolerogenic dendritic cells generated with different immunosuppressive cytokines induce antigen-specific anergy and regulatory properties in memory CD4+ T cells","volume":"184","author":"H Torres-Aguilar","journal-title":"J Immunol"},{"key":"ref35","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1016\/S0006-2952(00)00570-0","article-title":"Comparison of the potency of adenosine as an agonist at human adenosine receptors expressed in Chinese hamster ovary cells","volume":"61","author":"BB Fredholm","year":"2001","journal-title":"Biochem Pharmacol"},{"key":"ref36","doi-asserted-by":"crossref","first-page":"760","DOI":"10.1016\/j.micinf.2005.01.013","article-title":"Sand fly specificity of saliva-mediated protective immunity in Leishmania amazonensis-BALB\/c mouse model","volume":"7","author":"M Thiakaki","year":"2005","journal-title":"Microbes Infect"},{"key":"ref37","doi-asserted-by":"crossref","first-page":"110","DOI":"10.3389\/fimmu.2012.00110","article-title":"The immune response to sand fly salivary proteins and its influence on leishmania immunity","volume":"3","author":"R Gomes","year":"2012","journal-title":"Front Immunol"},{"key":"ref38","doi-asserted-by":"crossref","first-page":"1240","DOI":"10.1128\/IAI.72.3.1240-1247.2004","article-title":"Sand fly saliva enhances Leishmania amazonensis infection by modulating interleukin-10 production","volume":"72","author":"NB Norsworthy","year":"2004","journal-title":"Infect Immun"},{"key":"ref39","doi-asserted-by":"crossref","first-page":"2359","DOI":"10.1128\/IAI.01812-06","article-title":"Immunomodulatory effects of the Lutzomyia longipalpis salivary gland protein maxadilan on mouse macrophages","volume":"75","author":"TM Brodie","year":"2007","journal-title":"Infect Immun"},{"key":"ref40","doi-asserted-by":"crossref","first-page":"e873","DOI":"10.1371\/journal.pntd.0000873","article-title":"Lutzomyia longipalpis saliva triggers lipid body formation and prostaglandin E(2) production in murine macrophages","volume":"4","author":"T Araujo-Santos","year":"2010","journal-title":"PLoS Negl Trop Dis"},{"key":"ref41","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1016\/j.ejmech.2012.05.006","article-title":"Docking, synthesis and pharmacological activity of novel urea-derivatives designed as p38 MAPK inhibitors","volume":"54","author":"R de Oliveira Lopes","year":"2012","journal-title":"Eur J Med Chem"},{"key":"ref42","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1007\/s00011-011-0415-5","article-title":"Bosentan, an endothelin receptor antagonist, ameliorates collagen-induced arthritis: the role of TNF-alpha in the induction of endothelin system genes","volume":"61","author":"PB Donate","year":"2012","journal-title":"Inflamm Res"},{"key":"ref43","doi-asserted-by":"crossref","first-page":"1257","DOI":"10.1084\/jem.20062512","article-title":"Adenosine generation catalyzed by CD39 and CD73 expressed on regulatory T cells mediates immune suppression","volume":"204","author":"S Deaglio","year":"2007","journal-title":"J Exp Med"},{"key":"ref44","doi-asserted-by":"crossref","first-page":"1256","DOI":"10.1128\/IAI.01209-12","article-title":"5-Lipoxygenase activity increases susceptibility to experimental Paracoccidioides brasiliensis infection","volume":"81","author":"FS Tristao","year":"2013","journal-title":"Infect Immun"},{"key":"ref45","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1084\/jem.20020642","article-title":"Human CD4(+)CD25(+) regulatory, contact-dependent T cells induce interleukin 10-producing, contact-independent type 1-like regulatory T cells [corrected]","volume":"196","author":"D Dieckmann","year":"2002","journal-title":"J Exp Med"},{"key":"ref46","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1084\/jem.20020394","article-title":"Infectious tolerance: human CD25(+) regulatory T cells convey suppressor activity to conventional CD4(+) T helper cells","volume":"196","author":"H Jonuleit","year":"2002","journal-title":"J Exp Med"},{"key":"ref47","doi-asserted-by":"crossref","first-page":"2043","DOI":"10.1084\/jem.20110767","article-title":"Sustained suppression by Foxp3+ regulatory T cells is vital for infectious transplantation tolerance","volume":"208","author":"AR Kendal","year":"2011","journal-title":"J Exp Med"},{"key":"ref48","doi-asserted-by":"crossref","first-page":"264270","DOI":"10.1155\/2014\/264270","article-title":"Protective Role of 5-Lipoxigenase during Leishmania infantum Infection Is Associated with Th17 Subset","volume":"2014","author":"LA Sacramento","year":"2014","journal-title":"Biomed Res Int"},{"key":"ref49","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1084\/jem.194.6.719","article-title":"Anergy in peripheral memory CD4(+) T cells induced by low avidity engagement of T cell receptor","volume":"194","author":"S Mirshahidi","year":"2001","journal-title":"J Exp Med"},{"key":"ref50","doi-asserted-by":"crossref","first-page":"6074","DOI":"10.4049\/jimmunol.172.10.6074","article-title":"The tumoricidal activity of memory CD8+ T cells is hampered by persistent systemic antigen, but full functional capacity is regained in an antigen-free environment","volume":"172","author":"AT den Boer","year":"2004","journal-title":"J Immunol"},{"key":"ref51","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1186\/1744-8069-8-10","article-title":"Stimulation of peripheral kappa opioid receptors inhibits inflammatory hyperalgesia via activation of the PI3Kgamma\/AKT\/nNOS\/NO signaling pathway","volume":"8","author":"TM Cunha","year":"2012","journal-title":"Mol Pain"},{"key":"ref52","doi-asserted-by":"crossref","first-page":"1271","DOI":"10.1007\/s10096-011-1439-z","article-title":"Activation pattern of neutrophils from blood of elderly individuals with Candida-related denture stomatitis","volume":"31","author":"TH Gasparoto","year":"2012","journal-title":"Eur J Clin Microbiol Infect Dis"},{"key":"ref53","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1016\/j.imbio.2010.09.007","article-title":"Collagen induced arthritis (CIA) in mice features regulatory transcriptional network connecting major histocompatibility complex (MHC H2) with autoantigen genes in the thymus","volume":"216","author":"PB Donate","year":"2011","journal-title":"Immunobiology"},{"key":"ref54","doi-asserted-by":"crossref","first-page":"2765","DOI":"10.4049\/jimmunol.177.5.2765","article-title":"Cutting edge: Critical role for A2A adenosine receptors in the T cell-mediated regulation of colitis","volume":"177","author":"M Naganuma","year":"2006","journal-title":"J Immunol"},{"key":"ref55","doi-asserted-by":"crossref","first-page":"916","DOI":"10.1038\/414916a","article-title":"Role of G-protein-coupled adenosine receptors in downregulation of inflammation and protection from tissue damage","volume":"414","author":"A Ohta","year":"2001","journal-title":"Nature"},{"key":"ref56","doi-asserted-by":"crossref","first-page":"3931","DOI":"10.1172\/JCI63170","article-title":"Dendritic cells tolerized with adenosine A(2)AR agonist attenuate acute kidney injury","volume":"122","author":"L Li","year":"2012","journal-title":"J Clin Invest"}],"container-title":["PLOS Neglected Tropical Diseases"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pntd.0003600","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,6,8]],"date-time":"2024-06-08T07:41:32Z","timestamp":1717832492000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pntd.0003600"}},"subtitle":[],"editor":[{"given":"Alvaro","family":"Acosta-Serrano","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2015,4,7]]},"references-count":56,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2015,4,7]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pntd.0003600","relation":{},"ISSN":["1935-2735"],"issn-type":[{"value":"1935-2735","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,4,7]]}}}