Tug of war between<i>Acinetobacter baumannii</i>and host immune responses

Li, Fei-Ju; Starrs, Lora; Burgio, Gaétan

doi:10.1093/femspd/ftz004

Cited by 26 publications

(26 citation statements)

References 92 publications

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“…These data are consistent with previous study showing that some inflammatory cytokines, such as TNF-α, IL-1β, IL-6, IL-10, IL-17 and chemokines including CXCL1, CXCL2, CCL2, are significantly elevated in LAC-4-infected mice at 24 h post infection (9). It has been recognized that NLRP3 inflammasome/IL-1β signaling mediate lung pathology in A. baumannii pneumonia model, since NLRP3 and IL-1 receptordeficient mice showed reduced pathology (14,25,26). Consistent with these results, our RNA-seq data also suggest the critical role of inflammasome pathway, including IL-1β, NLRP3, NLRC4, ASC, caspase-1, and caspase-8 ( Table S1).…”

Section: Discussionmentioning

confidence: 96%

Transcriptome Profiling of Lung Innate Immune Responses Potentially Associated With the Pathogenesis of Acinetobacter baumannii Acute Lethal Pneumonia

Zeng

et al. 2020

Front. Immunol.

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Acinetobacter baumannii is one of the dominating causes of nosocomial pneumonia, however, very little is known about the host immune response associated with pathogenesis of A. baumannii infection. Here, we used a hypervirulent A. baumannii to establish an acute lethal pneumonia, supported by high bacterial burdens, severe inflammatory cells infiltration and lung damage. The lung transcriptome changes in response to A. baumannii lethal pneumonia were detected by RNA sequencing. The results showed that 6,288 host genes changed expression, with 3,313 upregulated genes and 2,975 downregulated genes. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis revealed that genes related to TNF, cytokine-cytokine receptor interaction, Toll-like receptor, NOD-like receptor, NF-κB, Jak-STAT, HIF-1 signaling pathways, apoptosis, and phagosome were significantly upregulated. Whereas, genes associated with PI3K-AKT signaling pathway, glycolysis/gluconeogenesis, amino acid and fatty acid metabolism were downregulated. Immune cell typing highlighted the inflammatory response of innate immune cells headed by neutrophils. The reliability of RNA sequencing results were verified with selected differentially expressed genes by real-time PCR. This work provides an insight into the pathogenesis of lethal A. baumannii lung infection.

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Section: Discussionmentioning

confidence: 96%

Transcriptome Profiling of Lung Innate Immune Responses Potentially Associated With the Pathogenesis of Acinetobacter baumannii Acute Lethal Pneumonia

Zeng

et al. 2020

Front. Immunol.

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“…A. baumannii has developed a number of specific and non-specific virulence factors for successful colonization and infection in the host. Detailed discussion of the potential roles and modes of action of these virulence factors are beyond the scope of this review and have been comprehensively reviewed elsewhere (Mortensen and Skaar, 2012 ; Lee et al, 2017 ; Weber et al, 2017 ; Wong et al, 2017 ; Harding et al, 2018 ; Li F.J. et al, 2018 ; Morris et al, 2019 ). Briefly, A. baumannii virulence factors play critical roles in serum/complement resistance, bacterial replication, cell adhesion and cytotoxicity, biofilm formation, immune evasion, and interaction with other bacteria during a polymicrobial infection (Lee et al, 2017 ; Wong et al, 2017 ; Harding et al, 2018 ; Morris et al, 2019 ).…”

Section: Virulence Factors and Pathogenesis Of A Baumanniimentioning

confidence: 99%

“…The majority of current studies on A. baumannii infections have focused on the molecular epidemiology of the infections, the distribution and mechanisms of antibiotic resistance, and the optimization of antibiotic treatment (Lee et al, 2017 ; Wong et al, 2017 ; Harding et al, 2018 ; Li F.J. et al, 2018 ; Morris et al, 2019 ). Relatively limited data are available on the host innate immune response to A. baumannii and its potential impact on the development of adaptive immunity against the infection.…”

Section: Introductionmentioning

confidence: 99%

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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“…The specific structures of A. baumannii facilitate the biofilm formation and bacteria colonization on skin, conjunctiva, oral, respiratory, rectal, and genitourinary tracts of patients by promoting bacterial adherence to various surfaces. [ 9 , 10 ] The colonization rate in critically ill patients detected with A. baumannii positive is as high as 44.3%. [ 6 ] The colonization on the respiratory tract can advance to pneumonia preferentially in immunocompromised patients.…”

Section: Introductionmentioning

confidence: 99%

Role of immunodeficiency in Acinetobacter baumannii associated pneumonia in mice

Liu

Xie

et al. 2020

Chinese Medical Journal

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Background Acinetobacter baumannii ( A. baumannii ) has become one of the most important opportunistic pathogens inducing nosocomial pneumonia and increasing mortality in critically ill patients recently. The interaction between A. baumannii infection and immune response can influence the prognosis of A. baumannii related pneumonia. The target of the present study was to investigate the role of immunodeficiency in A. baumannii induced pneumonia. Methods Male BALB/c mice were randomly divided into the normal immunity control (NIC) group, normal immunity infection (NIA) group, immune compromised control (CIC) group, and immune compromised infection (CIA) group ( n = 15 for each group). Intraperitoneal injection of cyclophosphamide and intranasal instillation of A. baumannii solution were used to induce compromised immunity and murine pneumonia, respectively. The mice were sacrificed at 6 and 24 h later and the specimens were collected for further tests. Seven-day mortality of mice was also assessed. Results After A. baumannii stimulation, the recruitment of neutrophils in mice with normal immunity increased sharply ( P = 0.030 at 6 h), while there was no significant raise of neutrophil counts in mice with compromised immune condition ( P = 0.092 at 6 h, P = 0.772 at 24 h). The Th cell polarization presented with pulmonary interleukin (IL)-4 and interferon (IFN)-γ level in response to the A. baumannii in CIA group were significantly depressed in comparison with in NIA group (IFN-γ: P = 0.003 at 6 h; P = 0.001 at 24 h; IL-4: P < 0.001 at 6 h; P < 0.001 at 24 h). The pulmonary conventional dendritic cell accumulation was even found to be inhibited after A. baumannii infection in immunocompromised mice ( P = 0.033). Correspondingly, A. baumannii associated pneumonia in mice with compromised immunity caused more early stage death, more severe histopathological impairment in lung. Conclusion A. baumannii could frustrate the immune response in immunocompromised conditions, and this reduced immune response is related to more severe lung injury and worse outcome in A. baumannii induced pneumonia.

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Tug of war betweenAcinetobacter baumanniiand host immune responses

Cited by 26 publications

References 92 publications

Transcriptome Profiling of Lung Innate Immune Responses Potentially Associated With the Pathogenesis of Acinetobacter baumannii Acute Lethal Pneumonia

Transcriptome Profiling of Lung Innate Immune Responses Potentially Associated With the Pathogenesis of Acinetobacter baumannii Acute Lethal Pneumonia

Host Innate Immune Responses to Acinetobacter baumannii Infection

Role of immunodeficiency in Acinetobacter baumannii associated pneumonia in mice

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