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

Abstract

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.

Host Innate Immune Responses to Acinetobacter baumannii Infection

“…They showed that genes related to TNF, cytokine-cytokine receptor interaction, TLRs, NOD-like receptor, NF-κB, Jak-STAT, HIF-1 signaling pathways, apoptosis, and phagosome were significantly upregulated whereas those associated with PI3K-AKT signaling pathway, glycolysis/gluconeogenesis, amino acid, and fatty acid metabolism were downregulated. The study also confirmed the importance of neutrophil-mediated inflammatory responses of innate immune cells in host innate defense against this pathogen (Zeng et al, 2020 ). However, further analysis of the kinetics of these changes will be needed to better define their contribution to the innate immunity against A. baumannii infection.…”

“…Their role in the pathogenesis and immunity against A. baumannii appears to be complex due to the multiple functions of most of the cytokines and chemokines. Indeed, Zeng et al ( 2020 ) recently analyzed the lung transcriptome changes in response to lethal intranasal infection with A. baumannii . They showed that genes related to TNF, cytokine-cytokine receptor interaction, TLRs, NOD-like receptor, NF-κB, Jak-STAT, HIF-1 signaling pathways, apoptosis, and phagosome were significantly upregulated whereas those associated with PI3K-AKT signaling pathway, glycolysis/gluconeogenesis, amino acid, and fatty acid metabolism were downregulated.…”

Giardia duodenalis and Its Secreted PPIB Trigger Inflammasome Activation and Pyroptosis in Macrophages through TLR4-Induced ROS Signaling and A20-Mediated NLRP3 Deubiquitination

“…Macrophages are primary effector cells of the innate immune system that form the first line of defense against microbial pathogens [ 42 ]. In this study, we found that Giardia and its secreted PPIB were able to induce macrophage pyroptosis and promote the release of the proinflammatory cytokines IL-1β and IL-18.…”

CCL28 modulates neutrophil responses during infection with mucosal pathogens

“…Moreover, the high survival of Ccl28 -/- mice infected with A. baumannii indicates that CCL28 can play a detrimental role for the host during pulmonary infection. While functioning neutrophils have been described to play a role in controlling Acinetobacter infection (García-Patiño et al, 2017; Grguric-Smith et al, 2015; Van Faassen et al, 2007), an exaggeration of neutrophil recruitment to the Acinetobacter -infected lung is deleterious (Yamada et al, 2013; Zeng et al, 2019, 2020). For example, in one relevant Acinetobacter pneumonia study, depletion of alveolar macrophages increased neutrophil infiltration, promoted extensive tissue damage, and increased systemic dissemination of Acinetobacter (Lee et al, 2020b).…”