Antimicrobial effector mechanisms are central to the function of the innate immune response in host defense against microbial pathogens. In humans, activation of Toll-like receptor 2/1 (TLR2/1) on monocytes induces a vitamin D dependent antimicrobial activity against intracellular mycobacteria. Here, we report that TLR activation of monocytes triggers induction of the defensin beta 4 gene (DEFB4), requiring convergence of the IL-1β and vitamin D receptor (VDR) pathways. TLR2/1 activation triggered IL-1β activity, involving the upregulation of both IL-1β and IL-1 receptor, and downregulation of the IL-1 receptor antagonist. TLR2/1L induction of IL-1β was required for upregulation of DEFB4, but not cathelicidin, whereas VDR activation was required for expression of both antimicrobial genes. The differential requirements for induction of DEFB4 and cathelicidin were reflected by differences in their respective promoter regions; the DEFB4 promoter had one vitamin D response element (VDRE) and two NF-κB sites, whereas the cathelicidin promoter had three VDREs and no NF-κB sites. Transfection of NF-κB into primary monocytes synergized with 1,25D3 in the induction of DEFB4 expression. Knockdown of either DEFB4 or cathelicidin in primary monocytes resulted in the loss of TLR2/1-mediated antimicrobial activity against intracellular mycobacteria. Therefore, these data identify a novel mechanism of host defense requiring the induction of IL-1β in synergy with vitamin D activation, for the TLR-induced antimicrobial pathway against an intracellular pathogen.

Leprosy provides a model to investigate mechanisms of immune regulation in humans, given that the disease forms a clinical-immunological spectrum. Here, we identified 13 miRNAs that were differentially expressed in the lesions of subjects with progressive lepromatous (L-lep) vs. the self-limited tuberculoid (T-lep) disease. Bioinformatic analysis revealed a significant enrichment of L-lep-specific miRNAs that preferentially target key immune genes downregulated in L-lep vs. T-lep lesions. The most differentially expressed miRNA in L-lep lesions, hsa-mir-21, was upregulated in M. leprae-infected monocytes. Hsa-mir-21, by downregulating toll-like receptor 2/1 (TLR2/1)-induced CYP27B1 and IL1B as well as upregulating IL-10, inhibited gene expression of the vitamin D-dependent antimicrobial peptides, CAMP and DEFB4A. Conversely, knockdown of hsa-mir-21 in M. leprae-infected monocytes enhanced expression of CAMP and DEFB4A and restored TLR2/1-mediated antimicrobial activity against M. leprae. Therefore, the ability of M. leprae to upregulate hsa-mir-21 targets multiple genes associated with the immunologically localized disease form, providing an effective mechanism to escape from the vitamin D-dependent antimicrobial pathway.

Background A well‐defined jawline is a critical component in the perception of facial attractiveness in both men and women. Dermal fillers offer a nonsurgical, temporary method of correcting mild‐to‐moderate mandibular bone resorption. Aims The authors discuss pertinent aspects of anatomy, pathophysiology of aging, patient evaluation, gender considerations, injection technique, and complications in jawline augmentation using injectable fillers. Methods A brief review of the literature surrounding jawline augmentation using injectable fillers in both men and women, as well as the authors’ experience in this area, is provided. Results Nonsurgical jawline augmentation using injectable fillers can be performed effectively and safely with adequate background knowledge of the regional anatomy and appropriate patient selection. The authors discuss both injection techniques in the published literature and their own approach. Potential complications are also reviewed. Conclusion Jawline rejuvenation is a key component to global facial aesthetic rejuvenation. Therefore, it is important for physicians to understand how to safely and effectively perform nonsurgical jawline rejuvenation using injectable fillers.

Black patients with advanced HNC are at increased risk of both disease progression and death from competing non-cancer mortality, particularly death from comorbid disease. Improved strategies to manage comorbid disease may increase the benefit of treatment intensification in black patients.

Poland's syndrome is a rare congenital condition characterized by absence of the pectoralis major muscle and a wide spectrum of associated ipsilateral chest wall and upper extremity anomalies. Associated dermatologic anomalies classically include pectoral and axillary alopecia, anhidrosis due to the absence of sweat glands, and deficiency in subcutaneous fat. Functional limitations are minimal, and thus surgical correction is primarily indicated for aesthetic purposes. Chest wall reconstruction typically involves transposition of a latissimus dorsi myocutaneous flap with or without a temporary subcutaneous tissue expander prior to surgical reconstruction. Using the PubMed database, a literature review was done on Poland's syndrome. We summarize the key features of Poland's syndrome, including the epidemiology, clinical presentation, pathogenesis, and management, and highlight the dermatologic associations reported in the literature.