Immune response profiles from humans experimentally exposed to Phlebotomus duboscqi bites
Cutaneous leishmaniasis is a neglected vector-borne parasitic disease prevalent in 92 countries with approximately one million new infections annually. Interactions between vector saliva and the human host alter the response to infection and outcome of disease. To characterize the human immunologica...
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Published in | Frontiers in immunology Vol. 15; p. 1335307 |
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Abstract | Cutaneous leishmaniasis is a neglected vector-borne parasitic disease prevalent in 92 countries with approximately one million new infections annually. Interactions between vector saliva and the human host alter the response to infection and outcome of disease.
To characterize the human immunological responses developed against saliva of
, a
vector, we repeatedly exposed the arms of 14 healthy U.S volunteers to uninfected
bites. Blood was collected a week after each exposure and used to assess total IgG antibodies against the proteins of
salivary gland homogenate (SGH) and the levels of IFN-gamma and IL-10 from peripheral blood mononuclear cells (PBMCs) stimulated with SGH or recombinant sand fly proteins. We analyzed skin punch biopsies of the human volunteer arms from the insect bite site and control skin site after multiple
exposures (four volunteers) using immunohistochemical staining.
A variety of immediate insect bite skin reactions were observed. Late skin reactions to insect bites were characterized by macular hyperpigmentation and/or erythematous papules. Hematoxylin and eosin staining showed moderate mononuclear skin infiltrate with eosinophils in those challenged recently (within 2 months), eosinophils were not seen in biopsies with recall challenge (6 month post bites). An increase in plasma antigen-specific IgG responses to SGH was observed over time. Western Blot results showed strong plasma reactivity to five
salivary proteins. Importantly, volunteers developed a cellular immunity characterized by the secretion of IFN-gamma upon PBMC stimulation with
SGH and recombinant antigens.
Our results demonstrate that humans mounted a local and systemic immune response against
salivary proteins. Specifically, PduM02/SP15-like and PduM73/adenosine deaminase recombinant salivary proteins triggered a Th1 type immune response that might be considered in future development of a potential
vaccine. |
---|---|
AbstractList | IntroductionCutaneous leishmaniasis is a neglected vector-borne parasitic disease prevalent in 92 countries with approximately one million new infections annually. Interactions between vector saliva and the human host alter the response to infection and outcome of disease.MethodsTo characterize the human immunological responses developed against saliva of Phlebotomus duboscqi, a Leishmania major (L. major) vector, we repeatedly exposed the arms of 14 healthy U.S volunteers to uninfected P. duboscqi bites. Blood was collected a week after each exposure and used to assess total IgG antibodies against the proteins of P. duboscqi salivary gland homogenate (SGH) and the levels of IFN-gamma and IL-10 from peripheral blood mononuclear cells (PBMCs) stimulated with SGH or recombinant sand fly proteins. We analyzed skin punch biopsies of the human volunteer arms from the insect bite site and control skin site after multiple P. duboscqi exposures (four volunteers) using immunohistochemical staining.ResultsA variety of immediate insect bite skin reactions were observed. Late skin reactions to insect bites were characterized by macular hyperpigmentation and/or erythematous papules. Hematoxylin and eosin staining showed moderate mononuclear skin infiltrate with eosinophils in those challenged recently (within 2 months), eosinophils were not seen in biopsies with recall challenge (6 month post bites). An increase in plasma antigen-specific IgG responses to SGH was observed over time. Western Blot results showed strong plasma reactivity to five P. duboscqi salivary proteins. Importantly, volunteers developed a cellular immunity characterized by the secretion of IFN-gamma upon PBMC stimulation with P. duboscqi SGH and recombinant antigens.DiscussionOur results demonstrate that humans mounted a local and systemic immune response against P. duboscqi salivary proteins. Specifically, PduM02/SP15-like and PduM73/adenosine deaminase recombinant salivary proteins triggered a Th1 type immune response that might be considered in future development of a potential Leishmania vaccine. Cutaneous leishmaniasis is a neglected vector-borne parasitic disease prevalent in 92 countries with approximately one million new infections annually. Interactions between vector saliva and the human host alter the response to infection and outcome of disease. To characterize the human immunological responses developed against saliva of , a vector, we repeatedly exposed the arms of 14 healthy U.S volunteers to uninfected bites. Blood was collected a week after each exposure and used to assess total IgG antibodies against the proteins of salivary gland homogenate (SGH) and the levels of IFN-gamma and IL-10 from peripheral blood mononuclear cells (PBMCs) stimulated with SGH or recombinant sand fly proteins. We analyzed skin punch biopsies of the human volunteer arms from the insect bite site and control skin site after multiple exposures (four volunteers) using immunohistochemical staining. A variety of immediate insect bite skin reactions were observed. Late skin reactions to insect bites were characterized by macular hyperpigmentation and/or erythematous papules. Hematoxylin and eosin staining showed moderate mononuclear skin infiltrate with eosinophils in those challenged recently (within 2 months), eosinophils were not seen in biopsies with recall challenge (6 month post bites). An increase in plasma antigen-specific IgG responses to SGH was observed over time. Western Blot results showed strong plasma reactivity to five salivary proteins. Importantly, volunteers developed a cellular immunity characterized by the secretion of IFN-gamma upon PBMC stimulation with SGH and recombinant antigens. Our results demonstrate that humans mounted a local and systemic immune response against salivary proteins. Specifically, PduM02/SP15-like and PduM73/adenosine deaminase recombinant salivary proteins triggered a Th1 type immune response that might be considered in future development of a potential vaccine. Introduction Cutaneous leishmaniasis is a neglected vector-borne parasitic disease prevalent in 92 countries with approximately one million new infections annually. Interactions between vector saliva and the human host alter the response to infection and outcome of disease. Methods To characterize the human immunological responses developed against saliva of Phlebotomus duboscqi , a Leishmania major (L. major) vector, we repeatedly exposed the arms of 14 healthy U.S volunteers to uninfected P. duboscqi bites. Blood was collected a week after each exposure and used to assess total IgG antibodies against the proteins of P. duboscqi salivary gland homogenate (SGH) and the levels of IFN-gamma and IL-10 from peripheral blood mononuclear cells (PBMCs) stimulated with SGH or recombinant sand fly proteins. We analyzed skin punch biopsies of the human volunteer arms from the insect bite site and control skin site after multiple P. duboscqi exposures (four volunteers) using immunohistochemical staining. Results A variety of immediate insect bite skin reactions were observed. Late skin reactions to insect bites were characterized by macular hyperpigmentation and/or erythematous papules. Hematoxylin and eosin staining showed moderate mononuclear skin infiltrate with eosinophils in those challenged recently (within 2 months), eosinophils were not seen in biopsies with recall challenge (6 month post bites). An increase in plasma antigen-specific IgG responses to SGH was observed over time. Western Blot results showed strong plasma reactivity to five P. duboscqi salivary proteins. Importantly, volunteers developed a cellular immunity characterized by the secretion of IFN-gamma upon PBMC stimulation with P. duboscqi SGH and recombinant antigens. Discussion Our results demonstrate that humans mounted a local and systemic immune response against P. duboscqi salivary proteins. Specifically, PduM02/SP15-like and PduM73/adenosine deaminase recombinant salivary proteins triggered a Th1 type immune response that might be considered in future development of a potential Leishmania vaccine. |
Author | Nurmukhambetova, Saule Valenzuela, Jesus G Hummer, Kelly Aronson, Naomi Wilkerson, Matthew D Ellis, Michael W Pazgier, Marzena Gomes, Regis Turiansky, George W Oliveira, Fabiano Meneses, Claudio Kamhawi, Shaden Ressner, Roseanne Abdeladhim, Maha Teixeira, Clarissa Lakhal-Naouar, Ines de Araujo, Fernanda Fortes Tolbert, W David |
AuthorAffiliation | 8 Department of Dermatology, Uniformed Services University of the Health Sciences , Bethesda, MD , United States 2 Henry M Jackson Foundation for the Advancement of Military Medicine , Bethesda, MD , United States 7 University of Toledo Medical Center , Toledo, OH , United States 1 Infectious Disease Division, Department of Medicine, Uniformed Services University of the Health Sciences , Bethesda, MD , United States 5 Department of Anatomy, Physiology and Genetics, Uniformed Services University of the Health Sciences , Bethesda, MD , United States 6 Center for Infectious Disease Research, Walter Reed Army Institute of Research , Silver Spring, MD , United States 3 Vector Molecular Biology Section, Laboratory of Malaria and Vector Research (LMVR), National Institutes of Allergy and Infectious Diseases, NIH , Rockville, MD , United States 4 Department of Biotechnology, Laboratory of Immunoparasitology, Oswaldo Cruz Foundation , Eusébio, CE , Brazil |
AuthorAffiliation_xml | – name: 7 University of Toledo Medical Center , Toledo, OH , United States – name: 2 Henry M Jackson Foundation for the Advancement of Military Medicine , Bethesda, MD , United States – name: 3 Vector Molecular Biology Section, Laboratory of Malaria and Vector Research (LMVR), National Institutes of Allergy and Infectious Diseases, NIH , Rockville, MD , United States – name: 1 Infectious Disease Division, Department of Medicine, Uniformed Services University of the Health Sciences , Bethesda, MD , United States – name: 5 Department of Anatomy, Physiology and Genetics, Uniformed Services University of the Health Sciences , Bethesda, MD , United States – name: 8 Department of Dermatology, Uniformed Services University of the Health Sciences , Bethesda, MD , United States – name: 4 Department of Biotechnology, Laboratory of Immunoparasitology, Oswaldo Cruz Foundation , Eusébio, CE , Brazil – name: 6 Center for Infectious Disease Research, Walter Reed Army Institute of Research , Silver Spring, MD , United States |
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Copyright | Copyright © 2024 de Araujo, Abdeladhim, Teixeira, Hummer, Wilkerson, Ressner, Lakhal-Naouar, Ellis, Meneses, Nurmukhambetova, Gomes, Tolbert, Turiansky, Pazgier, Oliveira, Valenzuela, Kamhawi and Aronson. Copyright © 2024 de Araujo, Abdeladhim, Teixeira, Hummer, Wilkerson, Ressner, Lakhal-Naouar, Ellis, Meneses, Nurmukhambetova, Gomes, Tolbert, Turiansky, Pazgier, Oliveira, Valenzuela, Kamhawi and Aronson 2024 de Araujo, Abdeladhim, Teixeira, Hummer, Wilkerson, Ressner, Lakhal-Naouar, Ellis, Meneses, Nurmukhambetova, Gomes, Tolbert, Turiansky, Pazgier, Oliveira, Valenzuela, Kamhawi and Aronson |
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Keywords | saliva vaccine P. duboscqi antigen immune response |
Language | English |
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Notes | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Edited by: Abhay Satoskar, The Ohio State University, United States These authors share senior authorship Reviewed by: Chaitenya Verma, The Ohio State University, United States Celio Geraldo Freire-de-Lima, Federal University of Rio de Janeiro, Brazil Present address: Fernanda Fortes de Araujo, Uniformed Services University of the Health Sciences, Bethesda, MD, United States |
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Snippet | Cutaneous leishmaniasis is a neglected vector-borne parasitic disease prevalent in 92 countries with approximately one million new infections annually.... Introduction Cutaneous leishmaniasis is a neglected vector-borne parasitic disease prevalent in 92 countries with approximately one million new infections... IntroductionCutaneous leishmaniasis is a neglected vector-borne parasitic disease prevalent in 92 countries with approximately one million new infections... |
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Title | Immune response profiles from humans experimentally exposed to Phlebotomus duboscqi bites |
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