The impact of TLR2 and aging on the humoral immune response to Staphylococcus aureus bacteremia in mice

Abstract Aging alters immunoglobulin production, affecting the humoral immune response. Toll-like receptor 2 (TLR2) recognizes Staphylococcus aureus (S. aureus) which causes bacteremia with high mortality in the elderly. To understand how TLR2 and aging affect the humoral immune response in bacterem...

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Main Authors: Priti Gupta, Zhicheng Hu, Pradeep Kumar Kopparapu, Meghshree Deshmukh, Tibor Sághy, Majd Mohammad, Tao Jin, Cecilia Engdahl
Format: Article
Language:English
Published: Nature Portfolio 2023-05-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-023-35970-3
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author Priti Gupta
Zhicheng Hu
Pradeep Kumar Kopparapu
Meghshree Deshmukh
Tibor Sághy
Majd Mohammad
Tao Jin
Cecilia Engdahl
author_facet Priti Gupta
Zhicheng Hu
Pradeep Kumar Kopparapu
Meghshree Deshmukh
Tibor Sághy
Majd Mohammad
Tao Jin
Cecilia Engdahl
author_sort Priti Gupta
collection DOAJ
description Abstract Aging alters immunoglobulin production, affecting the humoral immune response. Toll-like receptor 2 (TLR2) recognizes Staphylococcus aureus (S. aureus) which causes bacteremia with high mortality in the elderly. To understand how TLR2 and aging affect the humoral immune response in bacteremia, four groups of mice (wild type-young, wild type-old, TLR2−/−-young, and TLR2−/−-old) were used to analyze immunoglobulin levels in healthy conditions as well as 10 days after intravenous injection with S. aureus. We found that aging increased the levels of both IgM and IgG. Increased IgG in aged mice was controlled by TLR2. In bacteremia infection, aged mice failed to mount proper IgM response in both wild-type (WT) and TLR2−/− mice, whereas IgG response was impaired in both aged and TLR2−/− mice. Aged mice displayed reduced IgG1 and IgG2a response irrespective of TLR2 expression. However, impaired IgG2b response was only found in aged WT mice and not in TLR2−/− mice. Both aging and TLR2−/− increased the levels of anti-staphylococcal IgM in bacteremia. Aging increased sialylated IgG in WT mice but not in TLR2−/− mice. IgG sialylation was not affected by the infection in neither of the mice. In summary, aging increases all immunoglobulins except IgG1. However, aged mice fail to mount a proper antibody response to S. aureus bacteremia. TLR2 plays the regulatory role in IgG but not IgM response to infection.
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spelling doaj.art-6fee2f1e9119491b931625959ae85a152023-06-04T11:25:16ZengNature PortfolioScientific Reports2045-23222023-05-0113111110.1038/s41598-023-35970-3The impact of TLR2 and aging on the humoral immune response to Staphylococcus aureus bacteremia in micePriti Gupta0Zhicheng Hu1Pradeep Kumar Kopparapu2Meghshree Deshmukh3Tibor Sághy4Majd Mohammad5Tao Jin6Cecilia Engdahl7Department of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy, University of GothenburgDepartment of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy, University of GothenburgDepartment of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy, University of GothenburgDepartment of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy, University of GothenburgDepartment of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy, University of GothenburgDepartment of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy, University of GothenburgDepartment of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy, University of GothenburgDepartment of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy, University of GothenburgAbstract Aging alters immunoglobulin production, affecting the humoral immune response. Toll-like receptor 2 (TLR2) recognizes Staphylococcus aureus (S. aureus) which causes bacteremia with high mortality in the elderly. To understand how TLR2 and aging affect the humoral immune response in bacteremia, four groups of mice (wild type-young, wild type-old, TLR2−/−-young, and TLR2−/−-old) were used to analyze immunoglobulin levels in healthy conditions as well as 10 days after intravenous injection with S. aureus. We found that aging increased the levels of both IgM and IgG. Increased IgG in aged mice was controlled by TLR2. In bacteremia infection, aged mice failed to mount proper IgM response in both wild-type (WT) and TLR2−/− mice, whereas IgG response was impaired in both aged and TLR2−/− mice. Aged mice displayed reduced IgG1 and IgG2a response irrespective of TLR2 expression. However, impaired IgG2b response was only found in aged WT mice and not in TLR2−/− mice. Both aging and TLR2−/− increased the levels of anti-staphylococcal IgM in bacteremia. Aging increased sialylated IgG in WT mice but not in TLR2−/− mice. IgG sialylation was not affected by the infection in neither of the mice. In summary, aging increases all immunoglobulins except IgG1. However, aged mice fail to mount a proper antibody response to S. aureus bacteremia. TLR2 plays the regulatory role in IgG but not IgM response to infection.https://doi.org/10.1038/s41598-023-35970-3
spellingShingle Priti Gupta
Zhicheng Hu
Pradeep Kumar Kopparapu
Meghshree Deshmukh
Tibor Sághy
Majd Mohammad
Tao Jin
Cecilia Engdahl
The impact of TLR2 and aging on the humoral immune response to Staphylococcus aureus bacteremia in mice
Scientific Reports
title The impact of TLR2 and aging on the humoral immune response to Staphylococcus aureus bacteremia in mice
title_full The impact of TLR2 and aging on the humoral immune response to Staphylococcus aureus bacteremia in mice
title_fullStr The impact of TLR2 and aging on the humoral immune response to Staphylococcus aureus bacteremia in mice
title_full_unstemmed The impact of TLR2 and aging on the humoral immune response to Staphylococcus aureus bacteremia in mice
title_short The impact of TLR2 and aging on the humoral immune response to Staphylococcus aureus bacteremia in mice
title_sort impact of tlr2 and aging on the humoral immune response to staphylococcus aureus bacteremia in mice
url https://doi.org/10.1038/s41598-023-35970-3
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