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

Abstract

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.

Keywords: Acinetobacter baumannii; immune response; neutrophil; nosocomial; resistance.

Figure 1

Immune response to Acinetobacter baumannii infection. Antimicrobial peptides, produced by epithelial cells are one of the first bactericidal mechanisms against A. baumannii. At the same time, these antimicrobial peptides act as chemoattractants for neutrophils. A. baumannii possesses evasion mechanisms to avoid deposition of complement system components such as factor H and C3b. Epithelial cells recognize bacteria and secrete macrophage inflammatory protein 1 (MIP-1) to recruit monocytes. In turn, these monocytes, respond to A. baumannii secreting tumor necrosis factor (TNF-α), CXCL1, and CXCL2 to recruit neutrophils. A small percentage of bacteria evade neutrophil phagocytosis by adhering to the neutrophil surface and exploiting the migratory ability of these cells to disperse through the host. The chemokines CXCL1 and CXCL2, secreted in response to bacteria, as well as bacterial metabolites, serve as chemotactic factors for neutrophils. Once bacteria crossed through the epithelium, they can be recognized by natural killer (NK) cells, which respond by secreting CXCL1 and recruiting more neutrophils. Other innate immune cells, such as macrophages and dendritic cells (DCs), also recognize bacteria through toll-like receptor (TLR)-4 and TLR-2. Both DCs and macrophages produce proinflamatory cytokines in response to A. baumannii, and while macrophages secrete CXCL2 to recruit neutrophils, DCs process and present the bacteria to CD4⁺ T naïve cells polarizing toward a TH1 profile. The main mechanism through which A. baumannii infection can be controlled by macrophages is by the bactericidal effect of nitric oxide; while neutrophils kill A. baumannii by the production of reactive oxygen species. Because of its importance in responses that involve neutrophils, it has been considered, but not confirmed, the participation of IL-17 during A. baumannii infections. This cytokine could be produced by different cells including TH17, Tδγ, and type 3 innate lymphoid cells (ILC3), all induced in the presence of IL-23 secreted by macrophages, DCs, and epithelial cells.