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.