Tick salivary gland extract induces alpha‐gal syndrome in alpha‐gal deficient mice
Abstract Introduction Alpha‐gal syndrome (AGS) is characterized by delayed hypersensitivity to non‐primate mammalian meat in people having specific immunoglobulin E (sIgE) to the oligosaccharide galactose‐alpha‐1,3‐galactose. AGS has been linked to tick bites from Amblyomma americanum (Aa) in the U....
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Wiley
2021-09-01
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Series: | Immunity, Inflammation and Disease |
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Online Access: | https://doi.org/10.1002/iid3.457 |
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Article |
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DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Shailesh K. Choudhary Shahid Karim Onyinye I. Iweala Shivangi Choudhary Gary Crispell Surendra Raj Sharma Claire T. Addison Mike Kulis Brian H. Herrin Susan E. Little Scott P. Commins |
spellingShingle |
Shailesh K. Choudhary Shahid Karim Onyinye I. Iweala Shivangi Choudhary Gary Crispell Surendra Raj Sharma Claire T. Addison Mike Kulis Brian H. Herrin Susan E. Little Scott P. Commins Tick salivary gland extract induces alpha‐gal syndrome in alpha‐gal deficient mice Immunity, Inflammation and Disease alpha‐gal alpha‐gal knockout mice alpha‐gal syndrome Amblyomma americanum delayed allergic responses food allergy |
author_facet |
Shailesh K. Choudhary Shahid Karim Onyinye I. Iweala Shivangi Choudhary Gary Crispell Surendra Raj Sharma Claire T. Addison Mike Kulis Brian H. Herrin Susan E. Little Scott P. Commins |
author_sort |
Shailesh K. Choudhary |
title |
Tick salivary gland extract induces alpha‐gal syndrome in alpha‐gal deficient mice |
title_short |
Tick salivary gland extract induces alpha‐gal syndrome in alpha‐gal deficient mice |
title_full |
Tick salivary gland extract induces alpha‐gal syndrome in alpha‐gal deficient mice |
title_fullStr |
Tick salivary gland extract induces alpha‐gal syndrome in alpha‐gal deficient mice |
title_full_unstemmed |
Tick salivary gland extract induces alpha‐gal syndrome in alpha‐gal deficient mice |
title_sort |
tick salivary gland extract induces alpha‐gal syndrome in alpha‐gal deficient mice |
publisher |
Wiley |
series |
Immunity, Inflammation and Disease |
issn |
2050-4527 |
publishDate |
2021-09-01 |
description |
Abstract Introduction Alpha‐gal syndrome (AGS) is characterized by delayed hypersensitivity to non‐primate mammalian meat in people having specific immunoglobulin E (sIgE) to the oligosaccharide galactose‐alpha‐1,3‐galactose. AGS has been linked to tick bites from Amblyomma americanum (Aa) in the U.S. A small animal model of meat allergy is needed to study the mechanism of alpha‐gal sensitization, the effector phase leading to delayed allergic responses and potential therapeutics to treat AGS. Methods Eight‐ to ten‐weeks old mice with a targeted inactivation of alpha‐1,3‐galactosyltransferase (AGKO) were injected intradermally with 50 μg of Aa tick salivary gland extract (TSGE) on days 0, 7, 21, 28, 42, and 49. Total IgE and alpha‐gal sIgE were quantitated on Day 56 by enzyme‐linked immunosorbent assay. Mice were challenged orally with 400 mg of cooked pork kidney homogenate or pork fat. Reaction severity was assessed by measuring a drop in core body temperature and scoring allergic signs. Results Compared to control animals, mice treated with TSGE had 190‐fold higher total IgE on Day 56 (0.60 ± 0.12 ng/ml vs. 113.2 ± 24.77 ng/ml; p < 0.001). Alpha‐gal sIgE was also produced in AGKO mice following TSGE sensitization (undetected vs. 158.4 ± 72.43 pg/ml). Further, sensitized mice displayed moderate clinical allergic signs along with a drop in core body temperature of ≥2°C as an objective measure of a systemic allergic reaction. Interestingly, female mice had higher total IgE responses to TSGE treatment but male mice had larger declines in mean body temperature. Conclusion TSGE‐sensitized AGKO mice generate sIgE to alpha‐gal and demonstrate characteristic allergic responses to pork fat and pork kidney. In keeping with the AGS responses documented in humans, mice reacted more rapidly to organ meat than to high fat pork challenge. This mouse model establishes the central role of tick bites in the development of AGS and provides a small animal model to mechanistically study mammalian meat allergy. |
topic |
alpha‐gal alpha‐gal knockout mice alpha‐gal syndrome Amblyomma americanum delayed allergic responses food allergy |
url |
https://doi.org/10.1002/iid3.457 |
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doaj-82e482b101ea4315aa0d22825b5bacd42021-08-06T00:58:45ZengWileyImmunity, Inflammation and Disease2050-45272021-09-019398499010.1002/iid3.457Tick salivary gland extract induces alpha‐gal syndrome in alpha‐gal deficient miceShailesh K. Choudhary0Shahid Karim1Onyinye I. Iweala2Shivangi Choudhary3Gary Crispell4Surendra Raj Sharma5Claire T. Addison6Mike Kulis7Brian H. Herrin8Susan E. Little9Scott P. Commins10Division of Allergy, Immunology and Rheumatology, Thurston Arthritis Research Center University of North Carolina Chapel Hill North Carolina USACenter for Molecular and Cellular Biosciences, Department of Cell and Molecular Biology, School of Biological, Environmental, and Earth Sciences The University of Southern Mississippi Hattiesburg Mississippi USADivision of Allergy, Immunology and Rheumatology, Thurston Arthritis Research Center University of North Carolina Chapel Hill North Carolina USADivision of Allergy, Immunology and Rheumatology, Thurston Arthritis Research Center University of North Carolina Chapel Hill North Carolina USACenter for Molecular and Cellular Biosciences, Department of Cell and Molecular Biology, School of Biological, Environmental, and Earth Sciences The University of Southern Mississippi Hattiesburg Mississippi USACenter for Molecular and Cellular Biosciences, Department of Cell and Molecular Biology, School of Biological, Environmental, and Earth Sciences The University of Southern Mississippi Hattiesburg Mississippi USADivision of Allergy, Immunology and Rheumatology, Thurston Arthritis Research Center University of North Carolina Chapel Hill North Carolina USAUNC Food Allergy Initiative, Department of Pediatrics University of North Carolina Chapel Hill North Carolina USADepartment of Diagnostic Medicine and Pathobiology Kansas State University Manhattan Kansas USADepartment of Veterinary Pathobiology Oklahoma State University Stillwater Oklahoma USADivision of Allergy, Immunology and Rheumatology, Thurston Arthritis Research Center University of North Carolina Chapel Hill North Carolina USAAbstract Introduction Alpha‐gal syndrome (AGS) is characterized by delayed hypersensitivity to non‐primate mammalian meat in people having specific immunoglobulin E (sIgE) to the oligosaccharide galactose‐alpha‐1,3‐galactose. AGS has been linked to tick bites from Amblyomma americanum (Aa) in the U.S. A small animal model of meat allergy is needed to study the mechanism of alpha‐gal sensitization, the effector phase leading to delayed allergic responses and potential therapeutics to treat AGS. Methods Eight‐ to ten‐weeks old mice with a targeted inactivation of alpha‐1,3‐galactosyltransferase (AGKO) were injected intradermally with 50 μg of Aa tick salivary gland extract (TSGE) on days 0, 7, 21, 28, 42, and 49. Total IgE and alpha‐gal sIgE were quantitated on Day 56 by enzyme‐linked immunosorbent assay. Mice were challenged orally with 400 mg of cooked pork kidney homogenate or pork fat. Reaction severity was assessed by measuring a drop in core body temperature and scoring allergic signs. Results Compared to control animals, mice treated with TSGE had 190‐fold higher total IgE on Day 56 (0.60 ± 0.12 ng/ml vs. 113.2 ± 24.77 ng/ml; p < 0.001). Alpha‐gal sIgE was also produced in AGKO mice following TSGE sensitization (undetected vs. 158.4 ± 72.43 pg/ml). Further, sensitized mice displayed moderate clinical allergic signs along with a drop in core body temperature of ≥2°C as an objective measure of a systemic allergic reaction. Interestingly, female mice had higher total IgE responses to TSGE treatment but male mice had larger declines in mean body temperature. Conclusion TSGE‐sensitized AGKO mice generate sIgE to alpha‐gal and demonstrate characteristic allergic responses to pork fat and pork kidney. In keeping with the AGS responses documented in humans, mice reacted more rapidly to organ meat than to high fat pork challenge. This mouse model establishes the central role of tick bites in the development of AGS and provides a small animal model to mechanistically study mammalian meat allergy.https://doi.org/10.1002/iid3.457alpha‐galalpha‐gal knockout micealpha‐gal syndromeAmblyomma americanumdelayed allergic responsesfood allergy |