Toll-like receptor 2 promotes bacterial clearance during the initial stage of pulmonary infection with Acinetobacter baumannii

Kim, Chang‐Hwan; Kim, Dong‐Jae; Lee, Sang‐Jin; Jeong, Yu‐Jin; Kang, Min‐Jung; Lee, Jun‑Young; Choi, Jina; Kwon, Sun‐Jung; Park, Jae‐Hak; Park, Jong‐Hwan

doi:10.3892/mmr.2014.1966

Cited by 25 publications

(20 citation statements)

References 28 publications

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“…Additional evidence about the contribution of TLR-2 in the resolution of infection was given by March and colleagues, showing that the production of IL-8 by the epithelial cell line A549 was promoted through the recognition of A. baumannii by both TLR-4 and TLR-2 (36). Similarly, Kim and colleagues reported that TLR-2 contributes to the pulmonary clearance of A. baumannii (53). On the other hand, Knapp and colleagues found that TLR-2-deficient mice had lower bacterial burden at early stages of pulmonary infection as well as earlier polymorphonuclear cell recruitment to the lung when compared to WT mice (51).…”

Section: Cell Receptors Involved In the Recognition Of A Baumanniimentioning

confidence: 93%

“…Similar to other infections (49), two groups of PRRs, toll-like receptors (TLRs) and NOD receptors, have been implicated in the recognition of A. baumannii . While the role of TLR-2 and TLR-4 (two main TLRs recognizing PAMPs during bacterial infections) (50) has been widely explored in the context of A. baumannii infection (51–53), little is known about the recognition of A. baumannii through NOD receptors. A possible explanation is that A. baumannii is mainly considered an extracellular pathogen; however, as previously discussed, there are reports describing epithelial NOD1 and NOD2 activation by A. baumannii (37).…”

Section: Cell Receptors Involved In the Recognition Of A Baumanniimentioning

confidence: 99%

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The Immune Response against Acinetobacter baumannii, an Emerging Pathogen in Nosocomial Infections

2017

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Acinetobacter baumannii is the etiologic agent of a wide range of nosocomial infections, including pneumonia, bacteremia, and skin infections. Over the last 45 years, an alarming increase in the antibiotic resistance of this opportunistic microorganism has been reported, a situation that hinders effective treatments. In order to develop effective therapies against A. baumannii it is crucial to understand the basis of host–bacterium interactions, especially those concerning the immune response of the host. Different innate immune cells such as monocytes, macrophages, dendritic cells, and natural killer cells have been identified as important effectors in the defense against A. baumannii; among them, neutrophils represent a key immune cell indispensable for the control of the infection. Several immune strategies to combat A. baumannii have been identified such as recognition of the bacteria by immune cells through pattern recognition receptors, specifically toll-like receptors, which trigger bactericidal mechanisms including oxidative burst and cytokine and chemokine production to amplify the immune response against the pathogen. However, a complete picture of the protective immune strategies activated by this bacteria and its potential therapeutic use remains to be determined and explored.

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Section: Cell Receptors Involved In the Recognition Of A Baumanniimentioning

confidence: 93%

Section: Cell Receptors Involved In the Recognition Of A Baumanniimentioning

confidence: 99%

The Immune Response against Acinetobacter baumannii, an Emerging Pathogen in Nosocomial Infections

2017

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“…Likewise, in Staphylococcus aureus-induced lung infection, survival and bacterial burden in lungs and other distant organs of MyD88 knockout mice were similar compared with wild-type (WT) mice, although the levels of inflammatory cytokines and chemokines were diminished in knockout compared with WT mice (9). Furthermore, TLR2 mediates only partial resistance to other pathogens that cause lung infections, including Legionella pneumophila (10), Brucella melitensis (11), and Acinetobacter baumannii (12), suggesting the importance of TLR2-independent pathways for the complete protection of the host. Moreover, although TLR2 confers an effective protective response against the lethal intracellular pathogen Francisella tularensis after aerosolized infection of mice (13), this receptor was found to impair host defense and survival during pulmonary infection with another intracellular bacterium, Burkholderia pseudomallei (14).…”

Section: Toll-like Receptorsmentioning

confidence: 97%

Divergent Functions of Toll-like Receptors during Bacterial Lung Infections

Baral

Batra

Zemans

et al. 2014

Am J Respir Crit Care Med

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Lower respiratory tract infections caused by bacteria are a major cause of death in humans irrespective of sex, race, or geography. Indeed, accumulated data indicate greater mortality and morbidity due to these infections than cancer, malaria, or HIV infection. Successful recognition of, followed by an appropriate response to, bacterial pathogens in the lungs is crucial for effective pulmonary host defense. Although the early recruitment and activation of neutrophils in the lungs is key in the response against invading microbial pathogens, other sentinels, such as alveolar macrophages, epithelial cells, dendritic cells, and CD41 T cells, also contribute to the elimination of the bacterial burden. Pattern recognition receptors, such as Toll-like receptors (TLRs) and nucleotide-binding oligomerization domain-like receptors, are important for recognizing and responding to microbes during pulmonary infections. However, bacterial pathogens have acquired crafty evasive strategies to circumvent the pattern recognition receptor response and thus establish infection. Increased understanding of the function of TLRs and evasive mechanisms used by pathogens during pulmonary infection will deepen our knowledge of immunopathogenesis and is crucial for developing effective therapeutic and/or prophylactic measures. This review summarizes current knowledge of the multiple roles of TLRs in bacterial lung infections and highlights the mechanisms used by pathogens to modulate or interfere with TLR signaling in the lungs.

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“…Pattern recognition receptors, including Toll‐like receptors and Nod‐like receptors (NLRs), are critical for initiating host innate immune responses, resulting in the activation of immune cells and production of various inflammatory molecules to remove bacteria. Recent studies have indicated that Toll‐like receptors 2, 4 and 9 are involved in host defences against A. baumannii infection in vitro and in vivo …”

Section: Introductionmentioning

confidence: 99%

“…Recent studies have indicated that Toll-like receptors 2, 4 and 9 are involved in host defences against A. baumannii infection in vitro and in vivo. [7][8][9] Interleukin-1b (IL-1b) is a potent pro-inflammatory cytokine produced in various types of cells in response to infection, inflammation, injury or immunologic challenge. 10 Although IL-1b exerts a protective effect during infections, overexpression of this molecule can lead to tissue damage, and dysregulated inflammasome activation has been implicated in the pathogenesis of a variety of inflammatory diseases.…”

Section: Introductionmentioning

confidence: 99%

NLRP3 inflammasome mediates interleukin‐1β production in immune cells in response to Acinetobacter baumannii and contributes to pulmonary inflammation in mice

Kang

Kim

et al. 2017

Immunology

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Acinetobacter baumannii is a multi-drug resistant, Gram-negative bacteria and infection with this organism is one of the major causes of mortality in intensive care units. Inflammasomes are multiprotein oligomers that include caspase-1, and their activation is required for maturation of interleukin-1β (IL-1β). Inflammasome signalling is involved in host defences against various microbial infections, but the precise mechanism by which A. baumannii activates inflammasomes and the roles of relevant signals in host defence against pulmonary A. baumannii infection are unknown. Our results showed that NLRP3, ASC and caspase-1, but not NLRC4, are required for A. baumannii-induced production of IL-1β in macrophages. An inhibitor assay revealed that various pathways, including P2X7R, K efflux, reactive oxygen species production and release of cathepsins, are involved in IL-1β production in macrophages in response to A. baumannii. Interleukin-1β production in bronchoalveolar lavage (BAL) fluid was impaired in NLRP3-deficient and caspase-1/11-deficient mice infected with A. baumannii, compared with that in wild-type (WT) mice. However, the bacterial loads in BAL fluid and lungs were comparable between WT and NLRP3-deficient or caspase-1/11-deficient mice. The severity of lung pathology was reduced in NLRP3- deficient, caspase-1/11- deficient and IL-1-receptor-deficient mice, although the recruitment of immune cells and production of inflammatory cytokines and chemokines were not altered in these mice. These findings indicate that A. baumannii leads to the activation of NLRP3 inflammasome, which mediates IL-1β production and lung pathology.

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Toll-like receptor 2 promotes bacterial clearance during the initial stage of pulmonary infection with Acinetobacter baumannii

Cited by 25 publications

References 28 publications

The Immune Response against Acinetobacter baumannii, an Emerging Pathogen in Nosocomial Infections

The Immune Response against Acinetobacter baumannii, an Emerging Pathogen in Nosocomial Infections

Divergent Functions of Toll-like Receptors during Bacterial Lung Infections

NLRP3 inflammasome mediates interleukin‐1β production in immune cells in response to Acinetobacter baumannii and contributes to pulmonary inflammation in mice

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