Toll-Like Receptors 2 and 4 Modulate Pulmonary Inflammation and Host Factors Mediated by Outer Membrane Vesicles Derived from Acinetobacter baumannii

Marion, Chad R.; Lee, Jae‐Wook; Sharma, Lokesh; Park, Kyong-Su; Lee, Changjin; Liu, Wei; Liu, Pei; Feng, Jingjing; Gho, Yong Song; Cruz, Charles S. Dela

doi:10.1128/iai.00243-19

Cited by 32 publications

(41 citation statements)

References 43 publications

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“…The role of TLR4 in inflammatory diseases has been extensively studied 19,20 . In addition, the increasing amount of evidence pointed out that TLR4 signaling can promote injury, inflammation, and pulmonary fibrosis in acute or chronic lung injury mice model 21–23 . Generally, TLR4 could specially recognize Gram‐negative bacteria, such as LPS.…”

Section: Discussionmentioning

confidence: 99%

LncRNA UCA1 remits LPS‐engendered inflammatory damage through deactivation of miR‐499b‐5p/TLR4 axis

et al. 2020

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Neonatal pneumonia is a high neonatal mortality disease. The current research was designed to elucidate the modulatory function and feasible molecular mechanism of UCA1 in LPS-induced injury in pneumonia. Herein, LPS was applied to induce WI-38 cell inflammatory damage. We displayed that UCA1 was elevated in LPSinjured WI-38 cells. In the functional aspect, intervention of UCA1 evidently aggrandized cell viability in LPS-triggered WI-38 cells. In the meanwhile, elimination of UCA1 distinctly assuaged cell apoptosis concomitant with declined levels of proapoptotic proteins Bax and C-caspase-3, and ascended the expression of antiapoptotic protein Bcl-2. Subsequently, disruption of UCA1 manifestly restrained inflammatory damage as characterized by declination of multiple pro-inflammatory factors IL-1β, IL-6, and TNF-α in WI-38 cells under LPS circumstance. More importantly, we predicted and verified that UCA1 functioned as a ceRNA by efficaciously binding to miR-499b-5p thereby inversely adjusting miR-499b-5p expression. Interesting, TLR4 was identified as direct target of miR-499b-5p, and positively regulated by UCA1 through sponging miR-499b-5p. Mechanistically, absence of miR-499b-5p or restoration of TLR4 impeded the beneficial effects of UCA1 ablation on LPSstimulated apoptosis and inflammatory response. Collectively, these observations illuminated that UCA1 inhibition protected WI-38 cells against LPS-managed inflammatory injury and apoptosis process via miR-499b-5p/TLR4 crosstalk, which ultimately influencing the development of pneumonia.

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Section: Discussionmentioning

confidence: 99%

LncRNA UCA1 remits LPS‐engendered inflammatory damage through deactivation of miR‐499b‐5p/TLR4 axis

et al. 2020

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“…Several authors have described the release of membrane blebs from different pathogens, as well as their effects in vitro or in vivo (Holst et al, 2009; McConnell et al, 2011; Stevenson et al, 2018; Zhang et al, 2018). Recently, Marion et al (2019), showed pulmonary inflammation and neutrophil recruitment as well as cytokine production in mice inoculated with Acinetobacter baumannii membrane blebs intranasally. Also, membrane blebs from Aeromonas hydrophila induced B and T cell activation and the production of TNFα, IL-1β, and stimulated peripheral blood mononuclear cells producing IL-8 (Avila-Calderón et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

Proteomic Analysis of Membrane Blebs of Brucella abortus 2308 and RB51 and Their Evaluation as an Acellular Vaccine

et al. 2019

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Membrane blebs are released from Gram-negative bacteria, however, little is known about Brucella blebs. This work pursued two objectives, the first was to determine and identify the proteins in the membrane blebs by proteomics and in silico analysis. The second aim was to evaluate the use of membrane blebs of Brucella abortus 2308 and B. abortus RB51 as an acellular vaccine in vivo and in vitro. To achieve these aims, membrane blebs from B. abortus 2308 and RB51 were obtained and then analyzed by liquid chromatography coupled to mass spectrometry. Brucella membrane blebs were used as a “vaccine” to induce an immune response in BALB/c mice, using the strain B. abortus RB51 as a positive vaccine control. After subsequent challenge with B. abortus 2308, CFUs in spleens were determined; and immunoglobulins IgG1 and IgG2a were measured in murine serum by ELISA. Also, activation and costimulatory molecules induced by membrane blebs were analyzed in splenocytes by flow cytometry. Two hundred and twenty eight proteins were identified in 2308 membrane blebs and 171 in RB51 blebs, some of them are well-known Brucella immunogens such as SodC, Omp2b, Omp2a, Omp10, Omp16, and Omp19. Mice immunized with membrane blebs from rough or smooth B. abortus induced similar protective immune responses as well as the vaccine B. abortus RB51 after the challenge with virulent strain B. abortus 2308 (P < 0.05). The levels of IgG2a in mice vaccinated with 2308 membrane blebs were higher than those vaccinated with RB51 membrane blebs or B. abortus RB51 post-boosting. Moreover, mice immunized with 2308 blebs increased the percentage of activated B cells (CD19+CD69+) in vitro. Therefore, membrane blebs are potential candidates for the development of an acellular vaccine against brucellosis, especially those derived from the rough strains so that serological diagnostic is not affected.

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“…The reasons for the observed discrepancy is not clear but can be related to the differences in the LPS purity, the bacterial strains and the cells used in the studies. In addition, the pulmonary proinflammatory responses induced by intranasal inoculation of mice with A. baumannii OMVs were partially inhibited in TLR2-/- and TLR4-/- mice as compared to those of wild-type mice, further highlighting the important roles of those TLRs in A. baumannii -induced pulmonary inflammation in vivo (Marion et al, 2019 ).…”

Section: Host Innate Immune Responses To a Baumanniimentioning

confidence: 98%

Host Innate Immune Responses to Acinetobacter baumannii Infection

Chen

2020

Front. Cell. Infect. Microbiol.

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Acinetobacter baumannii has emerged as a major threat to global public health and is one of the key human pathogens in healthcare (nosocomial and community-acquired)-associated infections. Moreover, A. baumannii rapidly develops resistance to multiple antibiotics and is now globally regarded as a serious multidrug resistant pathogen. There is an urgent need to develop novel vaccines and immunotherapeutics as alternatives to antibiotics for clinical management of A. baumannii infection. However, our knowledge of host immune responses to A. baumannii infection and the identification of novel therapeutic targets are significantly lacking. This review highlights the recent advances and critical gaps in our understanding how A. baumannii interacts with the host innate pattern-recognition receptors, induces a cascade of inflammatory cytokine and chemokine responses, and recruits innate immune effectors (such as neutrophils and macrophages) to the site of infection for effective control of the infection. Such knowledge will facilitate the identification of new targets for the design and development of effective therapeutics and vaccines to fight this emerging threat.

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Toll-Like Receptors 2 and 4 Modulate Pulmonary Inflammation and Host Factors Mediated by Outer Membrane Vesicles Derived from Acinetobacter baumannii

Cited by 32 publications

References 43 publications

LncRNA UCA1 remits LPS‐engendered inflammatory damage through deactivation of miR‐499b‐5p/TLR4 axis

LncRNA UCA1 remits LPS‐engendered inflammatory damage through deactivation of miR‐499b‐5p/TLR4 axis

Proteomic Analysis of Membrane Blebs of Brucella abortus 2308 and RB51 and Their Evaluation as an Acellular Vaccine

Host Innate Immune Responses to Acinetobacter baumannii Infection

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