Biology subjects

Bohannon, J. K.

Publications and source records attributed to Bohannon, J. K..

2 recordsLinked to original sources

bioRxiv2024

Weight loss-induced adipose macrophage memory improves local Staphylococcus aureus clearance in male mice

Different stimuli can induce innate immune memory to improve pathogen defense or worsen cardiometabolic disease. However, it is less clear if the same stimuli can induce both the protective and detrimental effects of innate immune memory. We previously showed that weight loss induces innate immune memory in adipose macrophages that correlates with worsened diabetes risk after weight regain. In this study, we investigated the effect of weight loss on macrophage cytokine production and overall survival in a mouse model of infection. Male C57Bl/6J mice were put on high-fat or low-fat diets over 18 weeks to induce weight gain or weight loss. Lean mice served as controls. All mice were then infected IV with 2.5x10^6 CFU Staphylococcus aureus. Tissues were collected from 10 mice/group at day 3 and the remaining animals were followed for survival. Weight gain mice had the highest blood neutrophils and the highest bacterial burden in the kidney. However, there was no significant difference in survival. The weight loss group had the highest plasma TNF- and a significant reduction in bacterial burden in the adipose tissue that correlated with increased adipose macrophage cytokine production. Thus, weight loss-induced adipose macrophage memory may both improve local S.aureus clearance and worsen diabetes risk upon weight regain. Collectively, these findings support the notion that innate immune memory is an evolutionarily protective mechanism that also contributes to the development of cardiometabolic diseases.

immunology↗

bioRxiv2022

MyD88-Dependent Signaling Drives Toll-Like Receptor-Induced Trained Immunity in Macrophages

Immunocompromised populations are highly vulnerable to developing life-threatening infections. Strategies to protect patients with weak immune responses are urgently needed. Employing trained immunity, whereby innate leukocytes undergo reprogramming upon exposure to a microbial product and respond more robustly to subsequent infection, is a promising approach. Previously, we demonstrated that the TLR4 agonist monophosphoryl lipid A (MPLA) induces trained immunity and confers broad resistance to infection. TLR4 signals through both MyD88- and TRIF-dependent cascades, but the relative contribution of each pathway to induction of trained immunity is unknown. Here, we show that MPLA-induced resistance to Staphylococcus aureus infection is lost in MyD88-KO, but not TRIF-KO, mice. The MyD88-activating agonist CpG (TLR9 agonist), but not TRIF-activating Poly I:C (TLR3 agonist), protects against infection in a macrophage-dependent manner. MPLA- and CpG-induced augmentation of macrophage metabolism and antimicrobial functions is blunted in MyD88-, but not TRIF-KO, macrophages. Augmentation of antimicrobial functions occurs in parallel to metabolic reprogramming and is dependent, in part, on mTOR activation. Splenic macrophages from CpG-treated mice confirmed that TLR/MyD88-induced reprogramming occurs in vivo. TLR/MyD88-triggered metabolic and functional reprogramming was reproduced in human monocyte-derived macrophages. These data show that MyD88-dependent signaling is critical in TLR-mediated trained immunity.

immunology↗