[Skybird]

Cathelicidin.


https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7192829/

CONCLUSION

In this review, we highlight the roles of vitamin D-cathelicidin signaling in cell-autonomous protection, autophagy regulation, and immune response modulation in host cells against various pathogen infections and inflammatory diseases. Functional VDR signaling activation, which is associated with cathelicidin induction, is clearly the best-studied area in the field of vitamin D-mediated antimicrobial responses to eradicate a broad spectrum of pathogens. Cathelicidin is involved in shaping our immune system to promote cell-autonomous defense mechanisms, simultaneously maintaining a balance with inflammation during infection. Recent studies have revealed key roles for vitamin D-induced cathelicidin in the maintenance of homeostasis as an autophagy process that is closely regulated by other intracellular signaling pathways, including calcium and AMPK. Indeed, vitamin D-cathelicidin interacts with other effector systems such as autophagy and lysosomal function, possibly converging into a dedicated protective role by preventing excessive immune pathology against a variety of infections. Nevertheless, several aspects in this field are only beginning to be understood; many open questions remain, including how the vitamin D-cathelicidin axis interconnects with key innate effector systems (e.g., autophagy and lysosomal acidification) and which factors are critically involved in the coordinated control of innate and adaptive immunity to promote protective immune responses during various infections. Clearly, further research is needed to manipulate vitamin D-cathelicidin signaling in different biological contexts. Topics for further study include the exact function of vitamin D-antimicrobial immunity in patients with various infectious diseases at different clinical stages, considering genetic variation in VDR genes and sera vitamin D levels.


Despite continuing efforts to develop new antibiotics, multidrug-resistant infections are emerging as a major health burden worldwide, with high associated morbidity and mortality. The activation of autophagy by VDR signaling is anticipated as a promising host-directed therapeutic strategy, even against drug-resistant bacterial strains (129). Understanding the mechanisms by which vitamin D-cathelicidin regulates innate host defense systems, in the context of autophagy and immune pathways, is of prime importance for exploring strong candidates for host-directed therapeutics against diverse infectious diseases. Vitamin D is strongly clinically associated with acute respiratory tract infections, parallel to vitamin D status and incidences of airway infections (16). Current findings provide promising evidence for the protective effects of vitamin D on respiratory tract infections, including TB (16). To date, vitamin D supplemental therapy has been the most widely used potential treatment in TB clinical trials. However, further evidence of the cathelicidin levels and its efficacy as a prerequisite before vitamin D supplementation move into clinical routine in infectious diseases. Further translational knowledge about vitamin D-cathelicidin axis should be accumulated to support the clinical application of vitamin D in various acute and chronic infectious diseases for prevention and/or to offer improved outcomes.