Abstract:
Host-directed therapies have emerged as an innovative and promising approach in
tuberculosis (TB) treatment due to the observed limitations of current TB regimen
such as lengthy duration and emergence of drug resistance. Thus, we explored
the role of curdlan (beta glucan polysaccharide) as a novel strategy to activate
macrophages against Mycobacterium tuberculosis (Mtb). The aim of the study was
to investigate the role of curdlan in restricting the Mtb growth both in vitro and
in vivo. Further, the immunomodulatory potential of curdlan against Mtb and the
underlying mechanism is largely unknown. We found that curdlan treatment enhanced
the antigen presentation, pro-inflammatory cytokines, Mtb uptake and killing activity
of macrophages. In vivo studies showed that curdlan therapy significantly reduced
the Mtb burden in lung and spleen of mice. Administration of curdlan triggered the
protective Th1 and Th17 immunity while boosting the central and effector memory
response in Mtb infected mice. Curdlan mediated anti-Mtb activity is through signal
transducer and activator of transcription-1 (STAT-1), which regulates nitric oxide
(NO) production through inducible NO synthase (iNOS) induction; along with this
activation of nuclear factor kappa B (NF-κB) was also evident in Mtb infected
macrophages. Thus, we demonstrate that curdlan exerts effective anti-tuberculous
activity anti-tuberculous activity. It can be used as a potential host-directed therapy
against Mtb.
