Platelet aggregation responses to Salmonella Typhimurium are determined by host anti-Salmonella antibody levels
| Autor: | Rachel E Lamerton, Samantha J Montague, Marisol Perez-Toledo, Steve P Watson, Adam F Cunningham |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2024 |
| Předmět: | |
| Zdroj: | Platelets, Vol 35, Iss 1 (2024) |
| Druh dokumentu: | article |
| ISSN: | 09537104 1369-1635 0953-7104 |
| DOI: | 10.1080/09537104.2024.2437241 |
| Popis: | Invasive non-typhoidal Salmonella infections are responsible for >75 000 deaths/year and >500 000 cases/year globally. Seventy-five percent of these cases occur in Sub-Saharan Africa, an increasing number of which are from multi-drug resistant strains. Interactions between bacteria and platelets can lead to thrombus formation, which can be beneficial for control of infection (immunothrombosis), or harmful through uncontrolled inflammation and organ damage (thromboinflammation). It is unknown whether Salmonella Typhimurium can activate human platelets. To assess this, light transmission aggregometry was used to measure platelet activation by two different Salmonella Typhimurium strains in 26 healthy donors in platelet-rich plasma and washed platelets. In platelet-rich plasma, but not in washed platelets, Salmonella Typhimurium activated platelets in a donor- and strain-dependent manner mediated through the low affinity immune receptor FcγRIIA and the feedback agonists, ADP and thromboxane A2. Plasma swap studies between strong and weak responders demonstrated a plasma component was responsible for the variation between donors. Depletion of anti-Salmonella antibodies from plasma abolished Salmonella-induced platelet aggregation responses, and addition of polyclonal anti-Salmonella antibody allowed aggregation in washed platelets. Correlating levels of anti-Salmonella total IgG or the IgG1, IgG2, IgG3 and IgG4 subclasses to platelet responses revealed total IgG levels, rather than levels of individual subclasses, positively correlated with maximum platelet aggregation results, and negatively with lag times. Overall, we show that anti-Salmonella IgG antibodies are responsible for donor variation in platelet aggregation responses to Salmonella and mediate this activity through FcγRIIA. |
| Databáze: | Directory of Open Access Journals |
| Externí odkaz: |
|