Obesity hampers bacteria killing by human neutrophils.

Obesity is a disease associated with an increased risk of various medical complications, including cardiovascular problems, diabetes, and infectious diseases. The higher incidence of infections in individuals with obesity is likely due to impaired immune functions. Neutrophils deploy microbicidal functions. However, it is unclear whether neutrophils in individuals with obesity function effectively against infections. To evaluate whether neutrophils in obesity have dysfunctional antimicrobial functions, neutrophils from individuals with normal weight and from individuals with obesity were isolated, and their phenotype and microbicidal functions were assessed. Neutrophils from individuals with obesity had higher expression of CD66b, CD11b, CD15, CD14, CD18, and CD182 on their membranes. The higher expression of these molecules correlated with higher body mass index, suggesting that obesity is associated with neutrophil activation. Accordingly, the phorbol 12-myristate 13-acetate (PMA)-induced respiratory burst in neutrophils from individuals with obesity was greater than in those from individuals without obesity, whereas phagocytosis and PMA-induced NETosis were comparable between neutrophils from individuals with or without obesity, implying that neutrophil functions are not impaired by obesity. However, neutrophil extracellular trap formation of neutrophils from individuals with obesity was selectively reduced in response to Staphylococcus aureus. Nevertheless, the actual killing of these bacteria was similar between neutrophils from individuals with or without obesity. In contrast, neutrophils from individuals with obesity exhibited impaired killing of Pseudomonas aeruginosa and of Klebsiella quasipneumoniae. Together, these findings suggest obesity induces neutrophil activation but disrupts pathogen-specific antimicrobial mechanisms of neutrophils. This deficiency in pathogen clearance could explain the increased susceptibility to infections observed in individuals with obesity.