Research paperVitamin D reduces autophagy by regulating NF-κB resistance to Aspergillus fumigatus infection
Introduction
Vitamin D is well known for be important physiologically in terms of calcium homeostasis and bone health (Carlberg, 2019, Zittermann and Pilz, 2017). Vitamin D exerts biological functions by activating the vitamin D receptor (VDR), which increases calcium absorption in the small intestine and promotes mineralization of the bone (Bizzaro et al., 2017). In addition to endocrine effects, vitamin D has been shown to play a constructive role in immune and lung inflammation (Fletcher et al., 2019, Pincikova et al., 2017). Extrarenal 1α-hydroxylase is expressed in different immune system cells, including respiratory epithelium, dendritic cells and alveolar macrophages (AMs), and lymphocytes (Brett et al., 2018, Miraglia Del Giudice et al., 2018, Cantorna et al., 2015) It is also indicated that the lungs are also important for the production of vitamin D active organs. Local 1,25D3 plays a part in all aspects of immune regulation. Vitamin D immunologic effects include increased secretion of antimicrobial peptide cathelicidine, stopping chemokine production and maturation of dendritic cells, as well as changes in cell differentiation T (Zhao et al., 2017). These cellular effects play a crucial role in host resistance to pathogens (Georgieva et al., 2019), and lack of vitamin D can damage its immune activity (Wimalawansa and Vitamin, 2019, Dzik and Kaczor, 2019, Chang and Lee, 2019).
Autophagy is a common way of lysosome degradation in eukaryotic cells (Mushegian, 2017;10(471):). It plays a major role in maintaining normal cellular functions by degradation of excessive or abnormal intracellular proteins (Lu et al., 2019). It plays an important role in a variety of pathologies including diabetes, cancer and pathogenic infections. In addition, autophagy plays a major role in fungi infections (Lin et al., 2019). Importantly, autophagy is a critical factor in the various stages of infection, such as programmed cell death, pathogenic growth and sporulation (Abdel-Mohsen et al., 2018). In addition, recent studies have shown that NF-κB plays an important role in fungal infections (Nielsen et al., 2018). NF-κB is a nuclear transcription factor with a wide range of biological activities that control the expression of many genes including cytokines, transcription factors and stress-related oxidative enzymes, which are involved in various physiological and pathological processes of inflammation, oxidative stress and apoptosis(Yao et al., 2015, Zhou et al., 2019).
Based on the local production of active D-vitamin L in the lungs, it can also act as an immunomodulatory molecule instead of an obstruction, and autophagy is also associated with Candida albicans infection (Das et al., 2019, Suh et al., 2017, Del Pinto et al., 2017, Lim et al., 2015, Fraga-Silva et al., 2016). We speculate that lung resistance to A.fumigatus may be that vitamin D reduces the level of autophagy in the lung by regulating NF-κB. In this study, we tried to validate our hypothesis by giving mice different doses of vitamin D diet and observing the extent of pulmonary aspergillosis infection in mice.
Section snippets
Animals
The Animal Experimental Ethical Committee approved all the animals in the experiment at the First Affiliated Hospital of Anhui University of Science and Technology under university-approved protocols. We got a large BALB/c mouse (from Anhui Medical University). In the small animal care facility of Anhui University of Science and Technology, rats are enclosed in a pathogen-free environment. The mice were exposed to a 12-hour light/dark cycle and a certain diet and tap water were provided ad
Lack of vitamin D causes resistance to A. fumigatus
In this study, we used BALB/c mouse to study whether vitamin D deficiency resists resistance to Aspergillus fumigatus. After 8 weeks of nutrition, VitD- mice had significantly lower levels of 25-(OH) D3 compared with VitD + mice (Fig. 1, P < 0.01). Calcium and phosphorus concentrations in serum were similar between eight weeks (data not shown). In 8 weeks, no significant changes were observed in the mean body weight of VitD and VitD + groups (Fig. 2). The mice were infected with mycobacterial
Discussion
Our results show that the survival rate of Vitid-infected A. fumigatus mice has been reduced and the lung's extinction of the organism is impaired. Vitamin D has a deterrent effect on the bacterial load in the lung tissue. In vitro experiments showed that vitamin D inhibited the formation of excessive autophagy of Aspergillus fumigatus by regulating NF-κB. Lack of vitamin D can damage the lungs against A. fumigatus by autophagy. In vivo and in vitro experiments have shown that vitamin D can
Declaration of Competing Interest
The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Acknowledgments
We are grateful to the laboratory staffs for offering clinical, animal, and data sampling for this research. Thanks for the support of the 2018 key research and development plan project of Anhui Province (prevention and control of nosocomial infection of elderly patients and effect evaluation by nurses of class III class A hospitals in Anhui Province, No.: 1804 h08020289).
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