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Macrophage plasticity, cellular origin, and phenotypic heterogeneity are perpetual challenges for studies addressing the biology of this pivotal immune cell in development, homeostasis, and tissue remodeling/repair. Consequently, a myriad of macrophage subtypes has been described in these contexts. To facilitate the identification of functional macrophage subtypes in vivo, here we used a flow cytometry-based assay that allows for detailed phenotyping of macrophages engaged in extracellular matrix (ECM) degradation. Of the five macrophage subtypes identified in the remodeling dermis by using this assay, collagen degradation was primarily executed by Ly6C−CCR2+ and Ly6C−CCR2low macrophages via mannose receptor-dependent collagen endocytosis, while Ly6C+CCR2+ macrophages were the dominant fibrin-endocytosing cells. Unexpectedly, the CCL2/MCP1-CCR2 signaling axis was critical for both collagen and fibrin degradation, while collagen degradation was independent of IL-4Ra signaling. Furthermore, the cytokine GM-CSF selectively enhanced collagen degradation by Ly6C+CCR2+ macrophages. This study reveals distinct subsets of macrophages engaged in ECM turnover and identifies novel wound healing-associated functions for CCL2 and GM-CSF inflammatory cytokines. Keywords: Collagen degradation, Extracellular matrix endocytosis, Fibrin degradation, Interleukin-13, Mannose receptor/CD206, uPARAP/Endo180

Summary: Mucosal tissues are constantly exposed to the outside environment. They receive signals from the commensal microbiome and tissue‐specific triggers including alimentary and airborne elements and are tasked to maintain balance in the absence of inflammation and infection. Here, we present neutrophils as sentinel cells in mucosal immunity. We discuss the roles of neutrophils in mucosal homeostasis and overview clinical susceptibilities in patients with neutrophil defects. Finally, we present concepts related to specification of neutrophil responses within specific mucosal tissue microenvironments. [ABSTRACT FROM AUTHOR]

Queue length estimation is imperative as a tool of designing traffic characteristics of an intersection while queue length prediction enables to identify the traffic congestion in advance. This study was aimed to estimate the queue length at signalized intersections having heterogeneous traffic conditions. Furthermore, the study predicts the vehicle queue length of a different intersection with using the estimation results. Therefore, two case studies were conducted in two locations for the queue estimation and queue prediction respectively. The queue estimation study was conducted in a signalized pedestrian crossing in Malabe, Sri Lanka and the queue prediction in a signalized intersection in Armour Street, Sri Lanka where the vehicle density reflected the intense heterogeneity. Heterogeneous traffic conditions were defined as the diversified vehicle composition. The heterogeneity was assimilated with the consideration of Passenger Car Units (PCU) in the measurements of the traffic flow. The influential factors of the queue length were contemplated with the arrival flow, discharge flow and the signal configuration. The time-series analysis integrated the unrestricted Vector Auto Regression (VAR) models as the queue length and the other considered variables which depends on the time. Moreover, the results have indicated a higher accuracy in the queue estimation, practically applied for the prediction constituting to the traffic characteristics of the formed vehicle queue. [ABSTRACT FROM AUTHOR]

Summary: Periodontitis is a common human inflammatory disease. In this condition, microbiota trigger excessive inflammation in oral mucosal tissues surrounding the dentition, resulting in destruction of tooth‐supporting structures (connective tissue and bone). While susceptibility factors for common forms of periodontitis are not clearly understood, studies in patients with single genetic defects reveal a critical role for tissue neutrophils in disease susceptibility. Indeed, various genetic defects in the development, egress from the bone marrow, chemotaxis, and extravasation are clearly linked to aggressive/severe periodontitis at an early age. Here, we provide an overview of genetic defects in neutrophil biology that are linked to periodontitis. In particular, we focus on the mechanisms underlying Leukocyte Adhesion Deficiency‐I, the prototypic Mendelian defect of impaired neutrophil extravasation and severe periodontitis. [ABSTRACT FROM AUTHOR]

Purpose: Studies in patients with single gene mutations reveal the role of specific genes and pathways in human health and disease. In this sense, studies in patients with genetic defects leading to periodontitis become important toward the understanding of genetic factors linked to periodontitis susceptibility. WHIM syndrome (Warts, Hypogammaglobulinemia, Infections, and Myelokathexis syndrome) is an autosomal dominant syndrome caused by gain of function (GOF) mutations in the chemokine receptor CXCR4. While severe periodontitis in early life has been reported in multiple cases of WHIM syndrome, a comprehensive characterization of periodontal clinical status has not been performed in a large WHIM cohort to date. Furthermore, mechanisms underlying periodontitis susceptibility in WHIM syndrome are not fully delineated. The purpose of this study was to characterize the extent of periodontal pathogenesis in patients with WHIM Syndrome immune dysfunction comparted to age-gender matched healthy controls through clinical parameters. Methods: A cohort of WHIM patients (n=23) and age matched healthy volunteers (n=23) were clinically evaluated at the NIH hospital. Clinical parameters included probing depth, clinical attachment loss, bleeding upon probing, and missing teeth as well as radiographic evidence of bone loss. Results: Patients with WHIM syndrome present with increased susceptibility to periodontitis. Thirty percent of WHIM patients presented with severe disease. WHIM patients had significantly increased mean probing depths p<0.0001, clinical attachment loss p<0.0001, percentage of sites bleeding on probing p=0.0009 and number of missing teeth 3.65+4.6 compared to age/gender matched healthy volunteers 1.7+1.58. Conclusions: GOF mutations in CXCR4 lead to periodontitis susceptibility. Further studies are exploring mechanisms underlying this phenotype. [ABSTRACT FROM AUTHOR]