Interleukin-22 level is negatively correlated with neutrophil recruitment in the lungs in a Pseudomonas aeruginosa pneumonia model

Chronic lower respiratory tract infection withPseudomonas aeruginosais difficult to treat due to enhanced antibiotic resistance and decreased efficacy of drug delivery to destroyed lung tissue. To determine the potential for restorative immunomodulation therapies, we evaluated the effect of Toll-like receptor 4 (TLR4) stimulation on the host immune response toPseudomonasinfection in mice. We implanted sterile plastic tubes precoated withP. aeruginosain the bronchi of mice, administered the TLR4/MD2 agonistic monoclonal antibody UT12 intraperitoneally every week, and subsequently analyzed the numbers of viable bacteria and inflammatory cells and the levels of cytokines. We also performed flow cytometry-based phagocytosis and opsonophagocytic killing assaysin vitrousing UT12-treated murine peritoneal neutrophils. UT12-treated mice showed significantly enhanced bacterial clearance, increased numbers of Ly6G+neutrophils, and increased concentrations of macrophage inflammatory protein 2 (MIP-2) in the lungs (P< 0.05). Depletion of CD4+T cells eliminated the ability of the UT12 treatment to improve bacterial clearance and promote neutrophil recruitment and MIP-2 production. Additionally, UT12-pretreated peritoneal neutrophils exhibited increased opsonophagocytic killing activity via activation of the serine protease pathway, specifically neutrophil elastase activity, in a TLR4-dependent manner. These data indicated that UT12 administration significantly augmented the innate immune response against chronic bacterial infection, in part by promoting neutrophil recruitment and bactericidal function.

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IRF3 Inhibits Neutrophil Recruitment in Mice Infected with Pseudomonas aeruginosa

Inflammation ◽

10.1007/s10753-017-0517-5 ◽

2017 ◽

Vol 40 (3) ◽

pp. 735-744 ◽

Cited By ~ 2

Author(s):

Zhenghao Piao ◽

Haiying Yuan ◽

Cuili Wang ◽

Liyun Shi

Keyword(s):

Pseudomonas Aeruginosa ◽

Neutrophil Recruitment

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Role of Alveolar Macrophages in Initiation and Regulation of Inflammation in Pseudomonas aeruginosaPneumonia

Infection and Immunity ◽

10.1128/iai.66.7.3164-3169.1998 ◽

1998 ◽

Vol 66 (7) ◽

pp. 3164-3169 ◽

Cited By ~ 142

Author(s):

Kunihiko Kooguchi ◽

Satoru Hashimoto ◽

Atsuko Kobayashi ◽

Yoshihiro Kitamura ◽

Ichidai Kudoh ◽

...

Keyword(s):

Pseudomonas Aeruginosa ◽

Lung Injury ◽

High Mortality ◽

Alveolar Macrophages ◽

Late Effects ◽

Neutrophil Recruitment ◽

Bacterial Clearance ◽

Aerosol Inhalation ◽

Early Effects

ABSTRACT To evaluate the role of alveolar macrophages (AMs) in acutePseudomonas aeruginosa pneumonia in mice, AMs were depleted by aerosol inhalation of liposomes containing clodronate disodium. AM-depleted mice were then intratracheally infected with 5 × 105 CFU of P. aeruginosa. In addition to monitoring neutrophil recruitment and chemokine releases, lung injury was evaluated soon after infection (8 h) and at a later time (48 h). At 8 h, depletion of AMs reduced neutrophil recruitment, chemokine release, and lung injury. At 48 h, however, depletion of AMs decreased bacterial clearance and resulted in delayed movement of neutrophils from the site of inflammation with aggravated lung injury. With instillation of 5 × 107 CFU of bacteria, AM-depleted mice showed low mortality within 24 h of infection but high mortality at a later time, in contrast to non-AM-depleted mice. These results demonstrate that depletion of AMs has beneficial early effects but deleterious late effects on lung injury and survival in cases of P. aeruginosa pneumonia.

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Interleukin-22 regulates interferon lambda expression in a mice model of pseudomonas aeruginosa pneumonia

Molecular Immunology ◽

10.1016/j.molimm.2019.12.003 ◽

2020 ◽

Vol 118 ◽

pp. 52-59 ◽

Cited By ~ 2

Author(s):

Alexis Broquet ◽

Anissa Besbes ◽

Jérôme Martin ◽

Cédric Jacqueline ◽

Mickaël Vourc’h ◽

...

Keyword(s):

Pseudomonas Aeruginosa ◽

Mice Model ◽

Interleukin 22 ◽

Interferon Lambda ◽

Lambda Expression

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Faculty Opinions recommendation of Candida albicans airway exposure primes the lung innate immune response against Pseudomonas aeruginosa infection through innate lymphoid cell recruitment and interleukin-22-associated mucosal response.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.718157412.793489677 ◽

2014 ◽

Author(s):

Ulrich Schaible ◽

Yeojun Yun

Keyword(s):

Immune Response ◽

Pseudomonas Aeruginosa ◽

Candida Albicans ◽

Lymphoid Cell ◽

Innate Immune ◽

Innate Lymphoid Cell ◽

Cell Recruitment ◽

Interleukin 22 ◽

Mucosal Response ◽

Pseudomonas Aeruginosa Infection

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Trappin-2 Promotes Early Clearance of Pseudomonas aeruginosa through CD14-Dependent Macrophage Activation and Neutrophil Recruitment

American Journal Of Pathology ◽

10.2353/ajpath.2009.080746 ◽

2009 ◽

Vol 174 (4) ◽

pp. 1338-1346 ◽

Cited By ~ 27

Author(s):

Thomas S. Wilkinson ◽

Kevin Dhaliwal ◽

Thomas W. Hamilton ◽

Alexander F. Lipka ◽

Lesley Farrell ◽

...

Keyword(s):

Pseudomonas Aeruginosa ◽

Macrophage Activation ◽

Neutrophil Recruitment

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Dimethyl sulfoxide decreases interleukin-8-mediated neutrophil recruitment in the airways

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.1996.271.5.l838 ◽

1996 ◽

Vol 271 (5) ◽

pp. L838-L843 ◽

Cited By ~ 1

Author(s):

P. P. Massion ◽

A. Linden ◽

H. Inoue ◽

M. Mathy ◽

K. M. Grattan ◽

...

Keyword(s):

Pseudomonas Aeruginosa ◽

Epithelial Cells ◽

Dimethyl Sulfoxide ◽

Neutrophil Recruitment ◽

Interleukin 8 ◽

Bronchial Epithelial ◽

Anti Inflammatory

In this study, we investigated the role of dimethyl sulfoxide (DMSO) in inhibiting interleukin-8 (IL-8)-mediated neutrophil recruitment induced by Pseudomonas aeruginosa (PA) bacterial supernatant. First, we tested whether DMSO could inhibit IL-8 production induced by PA in human bronchial epithelial (16-HBE) cells in vitro. In these cells, exposure to PA or H2O2 induced IL-8 production dose dependently, an effect that was inhibited by 1% DMSO at both the protein and RNA level. Second, we tested whether DMSO could block the recruitment of neutrophils induced by PA in a bypassed segment of dog trachea in vivo. PA supernatant was placed in the tracheal segment for 6 h in four dogs, and neutrophil recruitment and IL-8 concentrations were measured in the superfusate. DMSO prevented the recruitment of neutrophils and IL-8 production induced by PA time dependently. The results suggest that DMSO may play an anti-inflammatory role in the airway by inhibiting IL-8 production in epithelial cells.

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Candida albicans Airway Exposure Primes the Lung Innate Immune Response against Pseudomonas aeruginosa Infection through Innate Lymphoid Cell Recruitment and Interleukin-22-Associated Mucosal Response

Infection and Immunity ◽

10.1128/iai.01085-13 ◽

2013 ◽

Vol 82 (1) ◽

pp. 306-315 ◽

Cited By ~ 34

Author(s):

Jean Baptiste Mear ◽

Philippe Gosset ◽

Eric Kipnis ◽

Emmanuel Faure ◽

Rodrigue Dessein ◽

...

Keyword(s):

Pseudomonas Aeruginosa ◽

Candida Albicans ◽

Lung Injury ◽

Molecular Mechanisms ◽

Lymphoid Cells ◽

Content Type ◽

Cell Recruitment ◽

Interleukin 22 ◽

Cellular Source ◽

Pseudomonas Aeruginosa Infection

ABSTRACTPseudomonas aeruginosaandCandida albicansare two pathogens frequently encountered in the intensive care unit microbial community. We have demonstrated thatC. albicansairway exposure protected againstP. aeruginosa-induced lung injury. The goal of the present study was to characterize the cellular and molecular mechanisms associated withC. albicans-induced protection. Airway exposure byC. albicansled to the recruitment and activation of natural killer cells, innate lymphoid cells (ILCs), macrophages, and dendritic cells. This recruitment was associated with the secretion of interleukin-22 (IL-22), whose neutralization abolishedC. albicans-induced protection. We identified, by flow cytometry, ILCs as the only cellular source of IL-22. Depletion of ILCs by anti-CD90.2 antibodies was associated with a decreased IL-22 secretion and impaired survival afterP. aeruginosachallenge. Our results demonstrate that the production of IL-22, mainly by ILCs, is a major and inducible step in protection againstP. aeruginosa-induced lung injury. This cytokine may represent a clinical target inPseudomonas aeruginosa-induced lung injury.

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