Sialokinin in mosquito saliva shifts human immune responses towards intracellular pathogens
Mosquito saliva is a mix of numerous proteins that are injected into the skin while the mosquito searches for a blood meal. While mosquito saliva is known to be immunogenic, the salivary components driving these immune responses, as well as the types of immune responses that occur, are not well char...
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ftdoajarticles:oai:doaj.org/article:9593b7b7ba3d4eb7b8d33bb468fd07b2 2023-05-15T15:15:51+02:00 Sialokinin in mosquito saliva shifts human immune responses towards intracellular pathogens Jennifer L. Spencer Clinton Megan B. Vogt Alexander R. Kneubehl Brianne M. Hibl Silke Paust Rebecca Rico-Hesse 2023-02-01T00:00:00Z https://doaj.org/article/9593b7b7ba3d4eb7b8d33bb468fd07b2 EN eng Public Library of Science (PLoS) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9897557/?tool=EBI https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 https://doaj.org/article/9593b7b7ba3d4eb7b8d33bb468fd07b2 PLoS Neglected Tropical Diseases, Vol 17, Iss 2 (2023) Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 article 2023 ftdoajarticles 2023-02-12T01:31:49Z Mosquito saliva is a mix of numerous proteins that are injected into the skin while the mosquito searches for a blood meal. While mosquito saliva is known to be immunogenic, the salivary components driving these immune responses, as well as the types of immune responses that occur, are not well characterized. We investigated the effects of one potential immunomodulatory mosquito saliva protein, sialokinin, on the human immune response. We used flow cytometry to compare human immune cell populations between humanized mice bitten by sialokinin knockout mosquitoes or injected with sialokinin, and compared them to those bitten by wild-type mosquitoes, unbitten, or saline-injected control mice. Humanized mice received 4 mosquito bites or a single injection, were euthanized after 7 days, and skin, spleen, bone marrow, and blood were harvested for immune cell profiling. Our results show that bites from sialokinin knockout mosquitoes induced monocyte and macrophage populations in the skin, blood, bone marrow, and spleens, and primarily affected CD11c- cell populations. Other increased immune cells included plasmacytoid dendritic cells in the blood, natural killer cells in the skin and blood, and CD4+ T cells in all samples analyzed. Conversely, we observed that mice bitten with sialokinin knockout mosquitoes had decreased NKT cell populations in the skin, and fewer B cells in the blood, spleen, and bone marrow. Taken together, we demonstrated that sialokinin knockout saliva induces elements of a TH1 cellular immune response, suggesting that the sialokinin peptide is inducing a TH2 cellular immune response during wild-type mosquito biting. These findings are an important step towards understanding how mosquito saliva modulates the human immune system and which components of saliva may be critical for arboviral infection. By identifying immunomodulatory salivary proteins, such as sialokinin, we can develop vaccines against mosquito saliva components and direct efforts towards blocking arboviral infections. Author summary ... Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic |
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Open Polar |
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Directory of Open Access Journals: DOAJ Articles |
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ftdoajarticles |
language |
English |
topic |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
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Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 Jennifer L. Spencer Clinton Megan B. Vogt Alexander R. Kneubehl Brianne M. Hibl Silke Paust Rebecca Rico-Hesse Sialokinin in mosquito saliva shifts human immune responses towards intracellular pathogens |
topic_facet |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
description |
Mosquito saliva is a mix of numerous proteins that are injected into the skin while the mosquito searches for a blood meal. While mosquito saliva is known to be immunogenic, the salivary components driving these immune responses, as well as the types of immune responses that occur, are not well characterized. We investigated the effects of one potential immunomodulatory mosquito saliva protein, sialokinin, on the human immune response. We used flow cytometry to compare human immune cell populations between humanized mice bitten by sialokinin knockout mosquitoes or injected with sialokinin, and compared them to those bitten by wild-type mosquitoes, unbitten, or saline-injected control mice. Humanized mice received 4 mosquito bites or a single injection, were euthanized after 7 days, and skin, spleen, bone marrow, and blood were harvested for immune cell profiling. Our results show that bites from sialokinin knockout mosquitoes induced monocyte and macrophage populations in the skin, blood, bone marrow, and spleens, and primarily affected CD11c- cell populations. Other increased immune cells included plasmacytoid dendritic cells in the blood, natural killer cells in the skin and blood, and CD4+ T cells in all samples analyzed. Conversely, we observed that mice bitten with sialokinin knockout mosquitoes had decreased NKT cell populations in the skin, and fewer B cells in the blood, spleen, and bone marrow. Taken together, we demonstrated that sialokinin knockout saliva induces elements of a TH1 cellular immune response, suggesting that the sialokinin peptide is inducing a TH2 cellular immune response during wild-type mosquito biting. These findings are an important step towards understanding how mosquito saliva modulates the human immune system and which components of saliva may be critical for arboviral infection. By identifying immunomodulatory salivary proteins, such as sialokinin, we can develop vaccines against mosquito saliva components and direct efforts towards blocking arboviral infections. Author summary ... |
format |
Article in Journal/Newspaper |
author |
Jennifer L. Spencer Clinton Megan B. Vogt Alexander R. Kneubehl Brianne M. Hibl Silke Paust Rebecca Rico-Hesse |
author_facet |
Jennifer L. Spencer Clinton Megan B. Vogt Alexander R. Kneubehl Brianne M. Hibl Silke Paust Rebecca Rico-Hesse |
author_sort |
Jennifer L. Spencer Clinton |
title |
Sialokinin in mosquito saliva shifts human immune responses towards intracellular pathogens |
title_short |
Sialokinin in mosquito saliva shifts human immune responses towards intracellular pathogens |
title_full |
Sialokinin in mosquito saliva shifts human immune responses towards intracellular pathogens |
title_fullStr |
Sialokinin in mosquito saliva shifts human immune responses towards intracellular pathogens |
title_full_unstemmed |
Sialokinin in mosquito saliva shifts human immune responses towards intracellular pathogens |
title_sort |
sialokinin in mosquito saliva shifts human immune responses towards intracellular pathogens |
publisher |
Public Library of Science (PLoS) |
publishDate |
2023 |
url |
https://doaj.org/article/9593b7b7ba3d4eb7b8d33bb468fd07b2 |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
PLoS Neglected Tropical Diseases, Vol 17, Iss 2 (2023) |
op_relation |
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9897557/?tool=EBI https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 https://doaj.org/article/9593b7b7ba3d4eb7b8d33bb468fd07b2 |
_version_ |
1766346192153739264 |