Vitamin D - A host directed autophagy mediated therapy for tuberculosis.
Periyasamy. Krisna Moorthi KM; Ranganathan. Uma Devi UD; Tripathy. Srikanth Prasad SP; Bethunaickan. Ramalingam R
Key Findings
- Vitamin D activates enzymes that increase production of the antimicrobial peptide LL‑37.
- LL‑37 enhances xenophagy, a form of autophagy that targets TB bacteria for destruction.
- Autophagy is regulated by pathways like ULK1/2, Beclin‑1, mTOR, and AMPK, and can be influenced by other micronutrients such as zinc and iron.
Practical Outcomes
- Consider maintaining adequate vitamin D levels (e.g., 2,000‑4,000 IU daily) to potentially support LL‑37‑mediated immunity, especially if you’re at risk for TB. Pairing vitamin D with zinc may further boost autophagy. This should complement, not replace, conventional TB treatment and you should consult a healthcare professional before changing supplementation.
Summary
The paper explains that vitamin D helps the body make a natural antimicrobial peptide called LL‑37, which boosts a cellular cleanup process called autophagy that can trap and destroy TB bacteria. While this is mostly a review of existing science, it suggests that getting enough vitamin D (and possibly zinc) could support your immune system’s ability to fight TB, though it’s not a substitute for standard TB drugs.
Abstract
According to the WHO report 2019, Tuberculosis (TB) is an ancient disease of humanity that is curable. TB has caused significant morbidity and mortality even in 2018. The etiological agent of TB, Mycobacterium tuberculosis (MTB) exploits its virulence factors to escape from host immunity and therapeutic drugs. Host Directed Therapy (HDT) is an adjunctive therapy where repurposed drugs, small molecules, vitamins, cytokines, and monoclonal antibodies are used to overcome the pathogen exploited pathways in the host. One of the HDTs, i.e. induction of autophagy is a highly regulated intracellular self-degradative process in which pathogens are sequestered in double-layered autophagosomes and targeted to the lysosome for degradation. Apart from the pathogen clearance, autophagy involves the release of nutrients during starvation, removal of damaged organelles and aggregated proteins, antigen presentation, tumor suppression, and anti-aging mechanisms. Xenophagy is a type of selective autophagy against microbes induced by ubiquitin receptors (p62/SQSTM1, NDP52, NBR1, OPTN, Parkin and Smurf proteins) after pathogen recognition. ULK1/2, Beclin-1, ATG5-ATG12-ATG16 L and LC-II-PE complexes along with two nutrient-sensing protein complexes, mTOR and AMPK activate autophagy mechanisms to limit infection. Pattern Recognition Receptors (PRRs) such as TLR2, recognize lipopolysaccharide (LPS) of MTB and triggers vitamin D<sub>3</sub> activating enzymes. Activated vitamin D<sub>3</sub> induces the synthesis of antimicrobial peptide, LL-37, which further enhances xenophagy. Apart from vitamin D, few micronutrients such as zinc and iron also regulate autophagy. In this review, we discuss current knowledge, advances and perspectives of autophagy against TB.
Study Information
pubmed
2020
2020-10-09T00:00:00.000Z
10.1016/j.molimm.2020.08.007
18
94