Neutrophils inform and shape immune responses. Toll-like receptors (TLRs) play an essential part in the perception of microbes and shape the complex host responses that occur during infection. The TLRs present on neutrophils play an indispensable role in neutrophil mediated pathogen recognition and elimination. This study was done to identify the role of significant TLRs in immune responses leading to differences in cytokine/chemokine release following stimulation. We evaluated the concentrations of various significant cytokines (IL-1β, TNF, MIP-1α, MCP-1 and IL-8) secreted by neutrophils from healthy donors and pulmonary tuberculosis patients following TLR ligand stimulation. TLR stimulation increased the release of such cytokines in both the groups. Thus it is noted that TLR stimulation of neutrophils definitely lead to increased cytokine response. Also, the release of all the studied cytokines are found to be greatly increased in patient neutrophils, affirming that neutrophils undergo secretory level modifications during tuberculosis infection.
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http://dx.doi.org/10.1016/j.humimm.2015.10.005 | DOI Listing |
Nat Commun
January 2025
Amgen Research, Amgen Inc., 720 Gateway Blvd, South San Francisco, CA, 94080, USA.
TASL is an immune adaptor that binds to the solute carrier SLC15A4 and facilitates activation of the transcription factor IRF5 during Toll-like receptor (TLR) signaling. Similar to IRF5 and SLC15A4, single nucleotide polymorphisms (SNPs) within TASL have been implicated in increased susceptibility to systemic lupus erythematosus (SLE) in patients. However, the biological function of TASL in vivo and how SLE-associated SNPs increase disease risk is unknown.
View Article and Find Full Text PDFInt J Biol Macromol
January 2025
Discipline of Pharmaceutical Sciences, College of Health Sciences, University of KwaZulu-Natal, Private Bag X54001, Durban, South Africa. Electronic address:
Sepsis, a life-threatening disruption, remains a significant global healthcare challenge that urgently needs novel strategies to improve management. This study aimed to develop multifunctional vancomycin-loaded polymersomes (VCM-HA-SIL-Ps) using a novel hyaluronic acid-silybin (HA-SIL) conjugate to target the TLR inflammatory pathway and enhance VCM's efficacy against bacterial sepsis. HA-SIL was synthesized and characterized by FT-IR, UV-Vis spectroscopy, and H NMR.
View Article and Find Full Text PDFComp Med
December 2024
1Tri-Institutional Training Program in Laboratory Animal Medicine and Science, Memorial Sloan Kettering Cancer Center, Weill Cornell Medicine, and The Rockefeller University, New York, New York.
Chlamydia muridarum (Cm) has reemerged as a moderately prevalent infectious agent in research mouse colonies. Despite its experimental use, few studies evaluate Cm's effects on immunocompetent mice following its natural route of infection. A Cm field isolate was administered (orogastric gavage) to 8-wk-old female BALB/cJ (C) mice.
View Article and Find Full Text PDFSci Adv
January 2025
Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
Mitochondrial electron transport chain (ETC) function modulates macrophage biology; however, mechanisms underlying mitochondria ETC control of macrophage immune responses are not fully understood. Here, we report that mutant mice with mitochondria ETC complex III (CIII)-deficient macrophages exhibit increased susceptibility to influenza A virus (IAV) and LPS-induced endotoxic shock. Cultured bone marrow-derived macrophages (BMDMs) isolated from these mitochondria CIII-deficient mice released less IL-10 than controls following TLR3 or TLR4 stimulation.
View Article and Find Full Text PDFEur J Med Chem
January 2025
Laboratory of Chemical Biology, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, Jilin, 130022, China; School of Applied Chemistry and Engineering, University of Science and Technology of China, Hefei, Anhui, 230026, China. Electronic address:
Substance use disorders (SUDs) present a critical global health challenge, as current treatment options often prove insufficient, particularly for substances like ketamine and methamphetamine. In this study, we developed a novel immunotherapeutic strategy utilizing protein-free, polymer-based vaccines, with hyperbranched polyethylenimine (Hb-PEI) as a carrier to enhance immune specificity and remove the production of non-specific antibodies. Haptens for ketamine and methamphetamine were covalently conjugated to the Hb-PEI carrier, along with the Toll-like receptor (TLR) 7/8 agonist 1V209, to stimulate targeted humoral immune responses.
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