Immune Netw.  2020 Apr;20(2):e12. 10.4110/in.2020.20.e12.

Vitamin D-Cathelicidin Axis: at the Crossroads between Protective Immunity and Pathological Inflammation during Infection

• Chung C
• Silwal P
• Kim I
• Modlin RL
• Jo EK

• KMID: 2500011
• DOI: http://doi.org/10.4110/in.2020.20.e12

Abstract

Vitamin D signaling plays an essential role in innate defense against intracellular microorganisms via the generation of the antimicrobial protein cathelicidin. In addition to directly binding to and killing a range of pathogens, cathelicidin acts as a secondary messenger driving vitamin D-mediated inflammation during infection. Recent studies have elucidated the biological and clinical functions of cathelicidin in the context of vitamin D signaling. The vitamin D-cathelicidin axis is involved in the activation of autophagy, which enhances antimicrobial effects against diverse pathogens. Vitamin D studies have also revealed positive and negative regulatory effects of cathelicidin on inflammatory responses to pathogenic stimuli. Diverse innate and adaptive immune signals crosstalk with functional vitamin D receptor signals to enhance the role of cathelicidin action in cell-autonomous effector systems. In this review, we discuss recent findings that demonstrate how the vitamin D-cathelicidin pathway regulates autophagy machinery, protective immune defenses, and inflammation, and contributes to immune cooperation between innate and adaptive immunity. Understanding how the vitamin D-cathelicidin axis operates in the host response to infection will create opportunities for the development of new therapeutic approaches against a variety of infectious diseases.

Keyword

Vitamin D; Cathelicidin; Infections; Autophagy; Immunity; Inflammation