5.3 - AnxA1 and bacterial infections
To date, most studies on AnxA1 during bacterial infections have focused on its endogenous role and the importance of its receptor in containing inflammation and promoting resolution. Limited data is available regarding the exogenous administration of AnxA1 as a potential therapy. For example, research has shown that mice lacking the FPR2 receptor (FPR2KO) were more susceptible to meningitis induced byStreptococcus suis (S. suis ), while treatment with AnxA1, which binds to FPR2, reduced bacterial burden in the brain, lowered the production of IL-6 and CXCL1, and decreased neutrophil infiltration into the brain (Ni et al., 2021). Beneficial effects of AnxA1 have also been observed in other bacterial infections. The absence of AnxA1 impaired the host response against Mycobacterium tuberculosis and resulted in a transient increase in bacterial burden in the spleen (Vanessa et al., 2015). Interestingly, the inhibition of Phosphodiesterase-4 (PDE-4) with Rolipram, combined with antibiotic treatment, reduced bacterial burden and inflammation during pneumococcal pneumonia in mice, and was associated with increased AnxA1 expression levels (Tavares et al., 2016). In a murine model of S. pneumoniae infection, Ac2-26 treatment decreased lung lesions and bacterial load in the lungs of wild-type (WT) mice, but this effect was not observed in FPR2KO mice, indicating that the beneficial effects of the AnxA1 mimetic peptide occur through the FPR2 receptor (Machado et al., 2020). AnxA1 has been found to bind to Vibrio cholerae (V. cholerae ) and Lactobacillaceae in the gut, and V. cholerae can interfere with AnxA1 dynamics by secreting proteases that cleave AnxA1 into different fragments, suggesting the importance of this molecule for the pathogen (Zoued et al., 2021). While these findings are intriguing, they are not conclusive, and they demonstrate that bacteria can also affect AnxA1 dynamics and modulate the capacity of the host to deal with pathogens through perturbations of the AnxA1/FPR2 signaling pathway.