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 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.

Local Immune Activation and Age Impact on Humoral Immunity in Mice, with a Focus on IgG Sialylation

“…In line with previous studies of Staphylococcus infection in mice [25] and elderly humans [26], we found an increase in the older mice in all types of circulating IgG and subtypes. Serum IgG subclass levels were shown to vary with inflammation and age, although it is not constant, as described in several studies [25,27,28]. In this study, IgG1 levels mainly increased following the immune challenge, like our previous study on the Staphylococcus challenge in mice [25].…”

“…It has been suggested that antigen-specific antibody response is predominantly decreased in older people [24]. However, consistent with our previous study in systemic bacteremia, where age did not alter the antigen-specific IgG [25], we show no differences between young and adult mice in mBSA-specific IgG.…”

“…They found that adults and older human individuals mainly responded with IgG2 antibodies against pneumococcal polysaccharides, regardless of vaccination. The agedependent alteration of IgG2b coincided with our previous results in Staphylococcusinduced mice [25]. Despite being the least abundant IgG subtype in mouse serum, IgG3 increases with infections [30], especially with protein antigens [31].…”

“…Serum IgG subclass levels were shown to vary with inflammation and age, although it is not constant, as described in several studies [25,27,28]. In this study, IgG1 levels mainly increased following the immune challenge, like our previous study on the Staphylococcus challenge in mice [25]. IgG1 is vital for promoting opsonization and may have a remarkable ability to interact with FcγRs and activate the immune system.…”

Exploring the role of bacterial virulence factors and host elements in septic arthritis: insights from animal models for innovative therapies

“…Nonetheless, our recent study, employing aging and TLR-2 deficient mice, disclosed that increased age stood out as the primary contributor to heightened mortality rates and changes in spleen weight ( Hu et al, 2023 ). Surprisingly, the severity of septic arthritis remained unaltered by aging, even though aged mice demonstrated an insufficient antibody response to S. aureus infection ( Gupta et al, 2023 ).…”