Neutrophil-Dependent Immunity During Pulmonary Infections and Inflammations

Effah, Clement Yaw; Drokow, Emmanuel Kwateng; Agboyibor, Clement; Ding, Lei; He, Sitian; Liu, Shaohua; Akorli, Senyo Yao; Nuamah, Emmanuel; Sun, Tongwen; Zhou, Xiaolei; Liu, Hong; Xu, Zhiwei; Feng, Feifei; Wu, Yongjun

doi:10.3389/fimmu.2021.689866

Cited by 17 publications

(10 citation statements)

References 335 publications

(291 reference statements)

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“…The rapid recruitment of leukocytes to the lungs after an infection is coordinated by the production of chemokines by the resident cells [ 30 ]. In agreement with the decrease in immune cells in the lungs of CD14-deficient mice, the amount of CXCL1, CCL2 and CCL3 chemokines was also reduced at 3 d.p.i.…”

Section: Resultsmentioning

confidence: 99%

CD14 signaling mediates lung immunopathology and mice mortality induced by Achromobacter xylosoxidans

et al. 2022

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Objective and design Our research aimed to investigate the role of CD14 in pulmonary infection by Achromobacter xylosoxidans in an experimental murine model. Methods C57Bl/6 or CD14-deficient mice were infected intratracheally with non-lethal inoculum of A. xylosoxidans . At times 1, 3 and 7 days after infection, lungs, bronchoalveolar lavage and blood were collected. CD14 gene expression was determined by RT-PCR. The bacterial load in the lungs was assessed by counting colony forming units (CFU). Cytokines, chemokines, lipocalin-2 and sCD14 were quantified by the ELISA method. Inflammatory infiltrate was observed on histological sections stained with HE, and leukocyte subtypes were assessed by flow cytometry. In another set of experiments, C57Bl/6 or CD14-deficient mice were inoculated with lethal inoculum and the survival rate determined. Results CD14-deficient mice are protected from A. xylosoxidans -induced death, which is unrelated to bacterial load. The lungs of CD14-deficient mice presented a smaller area of tissue damage, less neutrophil and macrophage infiltration, less pulmonary edema, and a lower concentration of IL-6, TNF-α, CXCL1, CCL2 and CCL3 when compared with lungs of C57Bl/6 mice. We also observed that A. xylosoxidans infection increases the number of leukocytes expressing mCD14 and the levels of sCD14 in BALF and serum of C57Bl/6-infected mice. Conclusions In summary, our data show that in A. xylosoxidans infection, the activation of CD14 induces intense pulmonary inflammatory response resulting in mice death. Supplementary Information The online version contains supplementary material available at 10.1007/s00011-022-01641-8.

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Section: Resultsmentioning

confidence: 99%

CD14 signaling mediates lung immunopathology and mice mortality induced by Achromobacter xylosoxidans

et al. 2022

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“…1 H NMR (400 MHz, DMSO-d 6 ): δ 7.50 (d, J = 6.9 Hz, 1H), 7.37−7.25 (m, 6H), 7.21 (d, J = 9.1 Hz, 3H), 7.18−7.09 (m, 3H), 3.84 (s, 3H). 13 (5). The title compound was synthesized from methanol following a similar procedure described for compound 1, and product 5 was obtained as a white solid (104 mg, yield 64%).…”

Section: ■ Experimental Sectionmentioning

confidence: 99%

“…Acute lung injury (ALI) is a lung disease characterized by bilateral pulmonary edema and hypoxemia, and its severe stage can develop into acute respiratory distress syndrome (ARDS) with a mortality rate of approximately 40% . During ALI pathogenesis, excessive proinflammatory cellsespecially neutrophilsmigrate and infiltrate into the inflammatory site and destroy the lung structure by releasing intracellular granules, proinflammatory cytokines, and reactive oxygen species (ROS). − Current agents for treating ALI, such as corticosteroids, antioxidants, or statins, remain uncertain in reducing the mortality rate . High-dose usage of the agents described above may even trigger undesired side effects .…”

Section: Introductionmentioning

confidence: 99%

Unsymmetrical Phosphodiesters as GPR84 Antagonists with High Blood Exposure for the Treatment of Lung Inflammation

Wang

Chen

et al. 2023

J. Med. Chem.

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GPR84 is a proinflammatory G protein-coupled receptor that mediates myeloid immune cell functions. Blocking GPR84 with antagonists is a promising approach for treating inflammatory and fibrotic diseases. Previously, a GPR84 antagonist 604c, with a symmetrical phosphodiester structure, has displayed promising efficacy in a mouse model of ulcerative colitis. However, the low blood exposure resulting from physicochemical properties prevented its uses in other inflammatory diseases. In this study, a series of unsymmetrical phosphodiesters with lower lipophilicity were designed and tested. The representative compound 37 exhibited a 100-fold increase in mouse blood exposure compared to 604c while maintaining in vitro activity. In a mouse model of acute lung injury, 37 (30 mg/kg, po) significantly reduced the infiltration of proinflammatory cells and the release of inflammatory cytokines and ameliorated pathological changes equally or more effectively than N-acetylcysteine (100 mg/kg, po). These findings suggest that 37 is a promising candidate for treating lung inflammation.

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“…Neutrophils can kill Spn intracellularly through phagocytosis but are better recognized for their diverse and highly specialized extracellular antimicrobial defenses mediated by degranulation (Amulic et al, 2012). Degranulation is a regulated process by which activated neutrophils release effectors, including cationic antimicrobial peptides, serine proteases, myeloperoxidase, and reactive oxygen species (ROS) (Effah et al, 2021). Neutrophils can also release DNA to trap bacteria in neutrophil extracellular traps (NETs) through a process known as NETosis (Effah et al, 2021).…”

Section: Introductionmentioning

confidence: 99%

“…Degranulation is a regulated process by which activated neutrophils release effectors, including cationic antimicrobial peptides, serine proteases, myeloperoxidase, and reactive oxygen species (ROS) (Effah et al, 2021). Neutrophils can also release DNA to trap bacteria in neutrophil extracellular traps (NETs) through a process known as NETosis (Effah et al, 2021). Finally, neutrophils play a critical role in regulation of inflammation through the production of cytokines which recruit additional leukocytes to the site of infection (Tecchio et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

Neutrophil Recruitment in Pneumococcal Pneumonia

Palmer

Kimmey

2022

Front. Cell. Infect. Microbiol.

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Streptococcus pneumoniae (Spn) is the primary agent of community-acquired pneumonia. Neutrophils are innate immune cells that are essential for bacterial clearance during pneumococcal pneumonia but can also do harm to host tissue. Neutrophil migration in pneumococcal pneumonia is therefore a major determinant of host disease outcomes. During Spn infection, detection of the bacterium leads to an increase in proinflammatory signals and subsequent expression of integrins and ligands on both the neutrophil as well as endothelial and epithelial cells. These integrins and ligands mediate the tethering and migration of the neutrophil from the bloodstream to the site of infection. A gradient of host-derived and bacterial-derived chemoattractants contribute to targeted movement of neutrophils. During pneumococcal pneumonia, neutrophils are rapidly recruited to the pulmonary space, but studies show that some of the canonical neutrophil migratory machinery is dispensable. Investigation of neutrophil migration is necessary for us to understand the dynamics of pneumococcal infection. Here, we summarize what is known about the pathways that lead to migration of the neutrophil from the capillaries to the lung during pneumococcal infection.

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Neutrophil-Dependent Immunity During Pulmonary Infections and Inflammations

Cited by 17 publications

References 335 publications

CD14 signaling mediates lung immunopathology and mice mortality induced by Achromobacter xylosoxidans

CD14 signaling mediates lung immunopathology and mice mortality induced by Achromobacter xylosoxidans

Unsymmetrical Phosphodiesters as GPR84 Antagonists with High Blood Exposure for the Treatment of Lung Inflammation

Neutrophil Recruitment in Pneumococcal Pneumonia

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