Table 1.
Research models used to study host responses against Acinetobacter baumannii.
| A. baumannii strain | Approach | Model/experimental design | Major findings | Reference |
|---|---|---|---|---|
| ATCC 17961 | In vivo | Bronchopneumonia | Neutropenia increases A. baumannii susceptibility as a result of delayed production of cytokines and chemokines | (14) |
| 1 × 107 CFU intranasally inoculated in 8–12 weeks old female C57BL/6 and BALB/c mice | ||||
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| A112-II-a (nephritis clinical isolate) | In vivo | Bronchopneumonia | Natural killer cells recruit neutrophils through KC production | (15) |
| 1 × 107–1 × 108 CFU intranasally inoculated in 8–10 weeks old female C57BL/6 mice | ||||
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| ATCC 17961 | In vivo | Bronchopneumonia | Delayed and reduced production of chemokines and cytokines promote severe bronchopneumonia | (16) |
| Intranasally inoculated 8–12 weeks old A/J and C57BL/6 female mice with 1 × 107–1 × 108 CFU | ||||
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| ATCC and clinical isolates: HUMC1, LAC-4, HUMAC4, HUMC5, HUMC6, C14, AB0061, AB0068, UH7807, 17978, R2, 31 (clone B), 125, 152 (clone A), AB0071, AB0072, AB0074, AB0093, METRO 9, UH2207, UH4907, UH5107, UH5207, UH6507, UH7007, UH7507, UH8107, UH8307, UH8407, UH9007, UH9707, AB7075 | In vivo/in vitro | In vivo: bacteremia. Intravenously infected C3H/FeJ mice with 1.5 × 107–8 × 108 CFU | Complement system, macrophages, and neutrophils are involved in the defense mechanisms against A. baumannii | (17) |
| In vitro: complement susceptibility in BALB/cJ mouse serum. Phagocytosis by the murine macrophage cell line RAW264.7 | ||||
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| 576, 4502, 5798, 6143, and 7215 clinical isolates | In vivo | Septicemia. Intraperitoneally inoculated 6–8 weeks old C57BL/6J, C3HeB/FeJ, and IL-17a−/− knockout mice with 2.15 × 106–9.2 × 106 CFU | Dispensable role for IL-17A to control A. baumannii septicemia | (18) |
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| 0057, 1422, 1611, 2098, 2231, 3559, and 7405 clinical isolates | In vivo | Wound infection | Neutropenia causes a more severe A. baumannii wound infection | (19) |
| Wound inoculated 6–8 weeks old BALB/c mice with 1 × 107 CFU | ||||
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| ATCC 17961 | In vivo | Bronchopneumonia. Intranasally inoculated 8–12 weeks old B6.129S-Cybbtm1⋅Din/J (NADPH oxidase-deficient [gp91phox−/−]), B6.129P2-Nos2tm1⋅Lau/J (inducible nitric oxide synthase-deficient [NOS2−/−]), and C57BL/6 female mice with 1 × 107 CFU | Indispensable role for the NADPH phagocyte oxidase to control replication and dissemination of A. baumannii | (22) |
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| ATCC 19606 | In vitro | Human blood neutrophils in the presence of 5 × 107 CFU | A. baumannii infection does not induce neutrophil extracellular traps formation | (23) |
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| ATCC 17978, ATCC 17978::GFP, 17978ΔgacS, 17978 pgacS, 17978ΔgacA, 17978 pgacA, 17978ΔpaaA, 17978 ppaa, 17978ΔcsuD, M2, M2ΔabaI, and M2 pabaI mutant | In vivo | Septicemia | The bacterial metabolite phenylacetate is chemotactic for neutrophils during A. baumannii infection | (26) |
| Intravenously infected zebra fish embryo with 1 × 103 CFU | ||||
| Intraperitoneally infected 6–8 weeks old BALB/c female mice with 5 × 104 CFU | ||||
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| ATCC 19606™ and AB5075, AB5711, AB#4, and AB4795 clinical isolates | In vitro | A. baumannii culture in the presence of LL-37 and its derived peptides | Bactericidal activity of LL-37 against A. baumannii | (27) |
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| ATCC 19606 | In vivo/in vitro | Bronchopneumonia | A. baumannii adheres to neutrophils to spread in the host and avoid bactericidal mechanisms of neutrophils | (31) |
| Intratracheally infected 6 weeks old C3H/HeN female mice with 5 × 107 CFU | ||||
| In vitro: adherence, transmigration assays, and cytokine production in human blood neutrophils cultured in the presence of bacteria | ||||
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| ATCC 19606 and 19606R [lipopolysaccharide (LPS)-deficient mutant] | In vitro | Murine macrophage cell line RAW264.7 and immortalized toll-like receptor (TLR)-2-deficient, TLR-4-deficient, and MyD88/Mal-deficient murine macrophages in the presence of bacteria | Increased susceptibility to LL-37 in LPS-deficient A. baumannii | (33) |
| Recognition of A. baumannii through TLR-2 | ||||
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| AB0057 and ATCC 17978 isolates | In vitro | Primary cultures of oral or skin epithelial cells in the presence of A. baumannii (MOI 100) | Induction of hBDs, hBD-2 and hBD-3 in epithelial cells as a response to A. baumannii | (35) |
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| 1514, 670, 1064, and 1327 clinical isolates | In vitro | A. baumannii (MOI 100) incubated with human lung epithelial cell line A549 (ATCC CCL185) or primary human airway epithelial cells | Involvement of TLR-2 and TLR-4 in A. baumannii recognition and IL-8 production via NFκB and mitogen-activated protein kinases | (36) |
| Induction of hBD-2 in response to bacteria | ||||
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| ATCC 19606™ | In vitro | Human lung epithelial cell line A549 (ATCC CCL185), Nod1-, Nod2-, or Rip2-knocked down THP-1-derived macrophages or NFκB-luciferase/hBD-2-luciferase expressing HEK293T cell line in the presence of A. baumannii (MOI 100) | A. baumannii recognition through nucleotide-binding oligomerization domain (NOD)1 and NOD2 and hBD-2-mediated bacterial clearance | (37) |
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| DAB021, KA10, 04P412, and 05KA010 clinical isolates | In vitro | A. baumannii incubated with human serum | Evasion of complement system through Omps-factor H binding | (38) |
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| LK10, LK15, LK18, LK41, LK49, LK80, and LK88 clinical isolates | In vitro | A. baumannii incubated with human serum | Ability of A. baumannii to be recognized by alternative complement pathway | (39) |
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| ATCC 19606, ATCC 17978, and 11CS, 15CS, 17CS, 25CS, 27CS, V754948 clinical isolates, and ΔcipA mutant | In vitro | A. baumannii incubated with human serum | Complement system evasion through CipA degradation of C3b | (40) |
| Human umbilical vein endothelial cell line cocultured with bacteria (MOI 100) | ||||
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| LK10, LK41, and LK88 clinical isolates, and LK41.3 (PKF-deficient mutant) | In vitro | A. baumannii incubated with human serum | Role of PKF in complement system evasion | (41) |
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| ATCC 17961 | In vivo/in vitro | Bronchopneumonia. Intranasally inoculated 8–12 weeks old BALB/c mice with 1 × 108 CFU | Role of macrophages in early stages of A. baumannii bronchopneumonia | (47) |
| In vitro: phagocytosis, bactericidal assay, and cytokine/chemokine production using the monocyte–macrophage J774A.1 cell line (ATCC TIB-67, J774) in the presence of A. baumannii (MOI 100) | ||||
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| ATCC 19606™ | In vitro | Outer membrane protein A (OmpA)-stimulated bone marrow derived-dendritic cells (DCs) | OmpA from A. baumannii induces DC activation and confers them the ability to polarize T CD4+ cells toward a TH1 phenotype | (48) |
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| RUH 2037 (pneumonia clinical isolate) | In vivo | Bronchopneumonia | Description of TLR-4 and CD14 in the control of A. baumannii pneumonia | (51) |
| 1 × 106–1 × 108 CFU intranasally inoculated in 7–9 weeks old C57/BL6, CD14−/−, TLR-4−/−, and TLR-2−/− mice | ||||
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| KCCM 35453 (ATCC 15150) | In vitro | Wild-type, TLR-2−/−, and TLR-4−/− bone marrow-derived macrophages and DCs cocultured with different MOI of bacteria | TLR-4-mediated cytokine and nitric oxide production in response to A. baumannii | (52) |
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| KCCM 35453 (ATCC 15150) | In vivo | Bronchopneumonia. Intranasally inoculated C57/BL6 and TLR-2−/− mice with 3 × 107 CFU | TLR-2 limits A. baumannii replication at early stages of pneumonia | (53) |
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| 4801, 4802, 4803, 4808, and 4809 clinical isolates | In vitro | A. baumannii-stimulated human monocyte THP-1, and human embryonic kidney HEK-293 TLR-2- and TLR-4-expressing cell lines | LPS from A. baumannii induces tumor necrosis factor (TNF-α) production in THP-1 cells | (54) |
| UV killed A. baumannii is recognized by TLR-2 and TLR-4 | ||||
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| HS-54, HJJA-9, HJJA-7, UC-25, HS-4 HJJA-8, and 95-52 clinical isolates | In vitro | A. baumannii-derived LPS incubated with splenic cells from 6 to 8 weeks old BALB/c mice | TNF-α induction and mitogenic capacity of LPS from A. baumannii | (58) |
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| ATCC 17978, HUMC1, HUMC4, HUMC5, HUMC6, and HUMC12 | In vivo | Septicemia | Induction of protective anti-A. baumannii and anti-OmpA antibodies by active and passive immunization with recombinant protein | (63) |
| Intravenous infection with 1 × 10–2 × 107 CFU in 10 weeks to >6 months old BALB/c streptozotocin-induced diabetic mice | Increased phagocytosis by specific anti-OmpA antibodies | |||
| Immunization. Subcutaneous administration of 3 µg of recombinant OmpA plus Al(OH)3 to BALB/c mice or passive immunization with immune serum | ||||
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| None (recombinant OmpA) | In vivo | Subcutaneous administration of 3, 30, or 100 µg of recombinant OmpA plus Al(OH)3 to BALB/c mice | Predominance of IgG1 antibody subtype and activation of IFN-γ, IL-4, and IL-17 producing splenocytes after immunization with OmpA | (64) |
| Induction of IFN-γ/IL-4 or IL-4 cytokine profile depending on the dose of antigen (OmpA) during immunization | ||||