Author:
Gupta Priti,Hu Zhicheng,Kopparapu Pradeep Kumar,Deshmukh Meghshree,Sághy Tibor,Mohammad Majd,Jin Tao,Engdahl Cecilia
Abstract
AbstractAging 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.
Funder
Rune och Ulla Amlövs Stiftelse för Neurologisk och Reumatologisk Forskning
Wilhelm and Martina Lundgren Foundation
E och K.G. Lennanders stipendiestiftelse
Sahlgrenska University Hospital Foundations
Inger Bendix Stiftelse för Medicinsk Forskning
Magnus Bergvalls Stiftelse
Vetenskapsrådet
Vatenskapsrådet
the ALF agreement
ALF agreement
Konung Gustav V Foundation
Tore Nilsson Foundation
the Swedish Association Against Rheumatism
OE Edla Johansson Foundation
Åke Wiberg Foundation
University of Gothenburg
Publisher
Springer Science and Business Media LLC