NKT cells play a limited role in the neutrophilic inflammatory responses and host defense to pulmonary infection with Pseudomonas aeruginosa

Kinjo, Takeshi; Nakamatsu, Masashi; Nakasone, Chikara; Yamamoto, Noriaki; Kinjo, Yuki; Miyagi, Kazuya; Uezu, Kaori; Nakamura, Kiwamu; Higa, Futoshi; Tateyama, Masao; Takeda, Kazuyoshi; Nakayama, Toshinori; Taniguchi, Masaru; Kaku, Mitsuo; Fujita, Jiro; Kawakami, Kazuyoshi

doi:10.1016/j.micinf.2006.07.016

Cited by 19 publications

(15 citation statements)

References 26 publications

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“…In this regard, our observation is in agreement with those from the previous studies showing that NKT cells play a negligible role in host immune protection in a number of models of pulmonary infections by mycobacteria and Pseudomonas (44 -47). It has been found that NKT-deficient mice did not show any significant difference in their ability to clear Pseudomonas aeruginosa, an extracellular Gram-negative bacterium, from the lungs compared with WT mice (46). Similarly, there was a minimum of recruitment of ␥␦ and conventional CD8 T cells to the airway lumen during S. aureus infection.…”

Section: Discussionmentioning

confidence: 99%

NK Cells Play a Critical Protective Role in Host Defense against Acute ExtracellularStaphylococcus aureusBacterial Infection in the Lung

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McCormick

Gill

et al. 2008

The Journal of Immunology

111

104

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Staphylococcus aureus remains a common cause of nosocomial bacterial infections and are often antibiotic resistant. The role of NK cells and IL-15 and their relationship in host defense against extracellular bacterial pathogens including S. aureus remain unclear. We have undertaken several approaches to address this issue using wild type (WT), IL-15 gene knock-out (KO), and NK cell-depleted mouse models. Upon pulmonary staphylococcal infection WT mice had markedly increased activated NK cells, but not NKT or γδ T cells, in the airway lumen that correlated with IL-15 production in the airway and with alveolar macrophages. In vitro exposure to staphylococcal products and/or coculture with lung macrophages directly activated NK cells. In contrast, lung macrophages better phagocytosed S. aureus in the presence of NK cells. In sharp contrast to WT controls, IL-15 KO mice deficient in NK cells were found to be highly susceptible to pulmonary staphylococcal infection despite markedly increased neutrophils and macrophages in the lung. In further support of these findings, WT mice depleted of NK cells were similarly susceptible to staphylococcal infection while they remained fully capable of IL-15 production in the lung at levels similar to those of NK-competent WT hosts. Our study thus identifies a critical role for NK cells in host defense against pulmonary extracellular bacterial infection and suggests that IL-15 is involved in this process via its indispensable effect on NK cells, but not other innate cells. These findings hold implication for the development of therapeutics in treating antibiotic-resistant S. aureus infection.

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Section: Discussionmentioning

confidence: 99%

NK Cells Play a Critical Protective Role in Host Defense against Acute ExtracellularStaphylococcus aureusBacterial Infection in the Lung

Small

McCormick

Gill

et al. 2008

The Journal of Immunology

111

104

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“…Previous studies examining whether CD1d-restricted NKT cells played a role in the clearance of P. aeruginosa from the lungs produced conflicting results (11,12). One of the major differences between these reports was the use of different inbred strains of mice (C57BL/6 in one and BALB/cJ in the other).…”

Section: Resultsmentioning

confidence: 99%

“…CD1d and the innate-like NKT cell subset have been demonstrated to play roles in a number of bacterial infections, including infections by P. aeruginosa and Streptococcus pneumoniae (11,12,27,28). While variability in NKT cell number and function as a consequence of the host genetic background is now well appreciated (13-16, 18, 29), less attention has been paid to how this variability might affect the contribution of NKT cells in infectiousdisease models.…”

Section: Discussionmentioning

confidence: 99%

“…Once activated, NKT cells can rapidly produce large amounts of a wide variety of cytokines and chemokines which have significant modulatory effects during the early stages of infection on the function of leukocytes of both the innate and adaptive arms of the immune system, including neutrophils and macrophages (8)(9)(10). Previous investigations into the role of NKT cells in the host response to P. aeruginosa infection of the lungs have yielded conflicting results, with one report demonstrating that NKT cells were critical in mediating clearance of lung P. aeruginosa (11), while another found little evidence of a role for NKT cells (12).…”

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confidence: 99%

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The Role of CD1d-Restricted NKT Cells in the Clearance of Pseudomonas aeruginosa from the Lung Is Dependent on the Host Genetic Background

et al. 2015

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dPseudomonas aeruginosa is an important human opportunistic pathogen, accounting for a significant fraction of hospital-acquired lung infections. CD1d-restricted NKT cells comprise an unusual innate-like T cell subset that plays important roles in both bacterial and viral infections. Previous reports have differed in their conclusions regarding the role of NKT cells in clearance of P. aeruginosa from the lung. Since there is significant strain-dependent variation in NKT cell number and function among different inbred strains of mice, we investigated whether the role of NKT cells was dependent on the host genetic background. We found that NKT cells did indeed play a critical role in the clearance of P. aeruginosa from the lungs of BALB/c mice but that they played no discernible role in clearance from the lungs of C57BL/6 mice. We found that the strain-dependent role of NKT cells was associated with significant strain-dependent differences in cytokine production by lung NKT cells and that impaired clearance of P. aeruginosa in BALB/c CD1d ؊/؊ mice was associated with an increase in neutrophil influx to the lung and increased levels of proinflammatory cytokines and chemokines after infection. Finally, we found that the role of alveolar macrophages was also dependent on the genetic background. These data provide further support for a model in which the unusually high level of variability in NKT cell number and function among different genetic backgrounds may be an important contributor to infectious-disease susceptibility and pathology. P seudomonas aeruginosa is a ubiquitous Gram-negative bacterium that is an important human opportunistic pathogen. P. aeruginosa infection is responsible for a significant fraction of hospital-acquired infections (1). It commonly affects patients with impaired lung function due to disease (e.g., cystic fibrosis) or mechanical ventilation. While neutrophils appear to be the principal mediators of host resistance to P. aeruginosa in the lung (2), evidence suggests that other leukocyte subsets of both the innate and adaptive arms of the immune system also play significant roles in the host clearance of Pseudomonas bacteria from the lungs (1, 3).CD1d-restricted NKT cells comprise an unusual innate-like ␣␤ T cell subset that plays important roles in both bacterial and viral infections (4, 5). NKT cells can be activated directly, through the recognition of glycolipids presented by CD1d (6), or indirectly, through interleukin-12 (IL-12)) and IL-18 produced upon recognition of pathogen-associated molecular patterns (PAMPs) by pattern recognition receptors (7). Once activated, NKT cells can rapidly produce large amounts of a wide variety of cytokines and chemokines which have significant modulatory effects during the early stages of infection on the function of leukocytes of both the innate and adaptive arms of the immune system, including neutrophils and macrophages (8-10). Previous investigations into the role of NKT cells in the host response to P. aeruginosa infection of the lungs have yi...

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“…However, the protective role of i NKT cells in HSV-1 infection still remains uncertain, with other groups reporting similar susceptibility to HSV-1 infection between CD1dKO and WT mice [37]. Such discrepancies are common in studies of i NKT cells in the context of other infections, including bacterial infections, for example infection with Pseudomonas aeruginosa [38, 39]. Discordant data have also been published for parasite infections, for example using Plasmodium species [40, 41].…”

Section: Role Of Inkt Cells In Host Defense Against Infectionsmentioning

confidence: 99%

The role of invariant natural killer T cells in microbial immunity

Kinjo

Kitano

Kronenberg

2013

Journal of Infection and Chemotherapy

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Invariant natural killer T cells (iNKT cells) are unique lymphocytes with characteristic features, such as expression of an invariant T cell antigen receptor (TCR) α chain, recognition of glycolipid antigens presented by CD1d molecules, and ability to rapidly produce large amounts of cytokines, including interferon-γ (IFNγ) and interleukin 4 (IL-4) upon TCR stimulation. Many studies have demonstrated that iNKT cells participate in immune response against diverse microbes, including bacteria, fungi, protozoan parasites and viruses. Generally, these cells play protective roles in host defense against infections. However, in some contexts they play pathogenic roles, by inducing or augmenting inflammation. Recent reports show that iNKT cells recognize glycolipid antigens from pathogenic bacteria including Streptococcus pneumoniae, and they contribute to host defense against infection. iNKT cell responses to these microbial glycolipid antigens are highly conserved between rodents and humans, suggesting that iNKT cells are evolutionally conserved because their invariant TCR is useful in detecting certain pathogens. Furthermore, glycolipid-mediated iNKT cell activation during immunization has adjuvant activity, enhancing humoral and cell-mediated responses. Therefore, iNKT cell activation is an attractive target for developing new vaccines for infectious diseases.

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NKT cells play a limited role in the neutrophilic inflammatory responses and host defense to pulmonary infection with Pseudomonas aeruginosa

Cited by 19 publications

References 26 publications

NK Cells Play a Critical Protective Role in Host Defense against Acute ExtracellularStaphylococcus aureusBacterial Infection in the Lung

NK Cells Play a Critical Protective Role in Host Defense against Acute ExtracellularStaphylococcus aureusBacterial Infection in the Lung

The Role of CD1d-Restricted NKT Cells in the Clearance of Pseudomonas aeruginosa from the Lung Is Dependent on the Host Genetic Background

The role of invariant natural killer T cells in microbial immunity

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