Toll-Like Receptor 9 Contributes to Defense Against Acinetobacter Baumannii Infection

Overview

Journal Infect Immun

Publisher American Society for Microbiology

Specialty Allergy & Immunology

Date 2015 Aug 5

PMID 26238713

Citations 28

Authors

Michael J Noto

Kelli L Boyd

William J Burns

Matthew G Varga

Richard M Peek Jr

Eric P Skaar

Affiliations

Soon will be listed here.

Abstract

Acinetobacter baumannii is a common nosocomial pathogen capable of causing severe diseases associated with significant morbidity and mortality in impaired hosts. Pattern recognition receptors, such as the Toll-like receptors (TLRs), play a key role in pathogen detection and function to alert the immune system to infection. Here, we examine the role for TLR9 signaling in response to A. baumannii infection. In a murine model of A. baumannii pneumonia, TLR9(-/-) mice exhibit significantly increased bacterial burdens in the lungs, increased extrapulmonary bacterial dissemination, and more severe lung pathology compared with those in wild-type mice. Following systemic A. baumannii infection, TLR9(-/-) mice have significantly increased bacterial burdens in the lungs, as well as decreased proinflammatory cytokine and chemokine production. These results demonstrate that TLR9-mediated pathogen detection is important for host defense against the opportunistic pathogen Acinetobacter baumannii.

Citing Articles

Multidrug resistant : A study on its pathogenesis and therapeutics.

Mukhopadhyay H, Bairagi A, Mukherjee A, Prasad A, Roy A, Nayak A Curr Res Microb Sci. 2025; 8():100331.

PMID: 39802320 PMC: 11718326. DOI: 10.1016/j.crmicr.2024.100331.

Virulence Factors and Pathogenicity Mechanisms of in Respiratory Infectious Diseases.

Yao Y, Chen Q, Zhou H Antibiotics (Basel). 2023; 12(12).

PMID: 38136783 PMC: 10740465. DOI: 10.3390/antibiotics12121749.

Deciphering the virulence factors, regulation, and immune response to infection.

Shadan A, Pathak A, Ma Y, Pathania R, Singh R Front Cell Infect Microbiol. 2023; 13:1053968.

PMID: 36968113 PMC: 10038080. DOI: 10.3389/fcimb.2023.1053968.

Novel adjuvant nano-vaccine induced immune response against Acinetobacter baumannii.

Piri-Gharaghie T, Doosti A, Mirzaei S AMB Express. 2023; 13(1):31.

PMID: 36905472 PMC: 10008545. DOI: 10.1186/s13568-023-01531-0.

Bacterial Community Characteristics Shaped by Artificial Environmental PM2.5 Control in Intensive Broiler Houses.

Wang W, Dang G, Khan I, Ye X, Liu L, Zhong R Int J Environ Res Public Health. 2023; 20(1).

PMID: 36613044 PMC: 9819255. DOI: 10.3390/ijerph20010723.

References

Qiu H, KuoLee R, Harris G, van Rooijen N, Patel G, Chen W . Role of macrophages in early host resistance to respiratory Acinetobacter baumannii infection. PLoS One. 2012; 7(6):e40019. PMC: 3386929. DOI: 10.1371/journal.pone.0040019. View

Qureshi Z, Hittle L, OHara J, Rivera J, Syed A, Shields R . Colistin-resistant Acinetobacter baumannii: beyond carbapenem resistance. Clin Infect Dis. 2015; 60(9):1295-303. PMC: 4462660. DOI: 10.1093/cid/civ048. View

Parker D, Prince A . Staphylococcus aureus induces type I IFN signaling in dendritic cells via TLR9. J Immunol. 2012; 189(8):4040-6. PMC: 3466375. DOI: 10.4049/jimmunol.1201055. View

Hood M, Mortensen B, Moore J, Zhang Y, Kehl-Fie T, Sugitani N . Identification of an Acinetobacter baumannii zinc acquisition system that facilitates resistance to calprotectin-mediated zinc sequestration. PLoS Pathog. 2012; 8(12):e1003068. PMC: 3516566. DOI: 10.1371/journal.ppat.1003068. View

Hood M, Becker K, Roux C, Dunman P, Skaar E . genetic determinants of intrinsic colistin tolerance in Acinetobacter baumannii. Infect Immun. 2012; 81(2):542-51. PMC: 3553813. DOI: 10.1128/IAI.00704-12. View

Schneberger D, Caldwell S, Kanthan R, Singh B . Expression of Toll-like receptor 9 in mouse and human lungs. J Anat. 2013; 222(5):495-503. PMC: 3633339. DOI: 10.1111/joa.12039. View

Hood M, Uzhachenko R, Boyd K, Skaar E, Ivanova A . Loss of mitochondrial protein Fus1 augments host resistance to Acinetobacter baumannii infection. Infect Immun. 2013; 81(12):4461-9. PMC: 3837987. DOI: 10.1128/IAI.00771-13. View

Kim S, Min Y, Cheong J, Kim J, Kim S, Ku N . Incidence and risk factors for carbapenem- and multidrug-resistant Acinetobacter baumannii bacteremia in hematopoietic stem cell transplantation recipients. Scand J Infect Dis. 2013; 46(2):81-8. DOI: 10.3109/00365548.2013.857042. View

Bist P, Dikshit N, Koh T, Mortellaro A, Tan T, Sukumaran B . The Nod1, Nod2, and Rip2 axis contributes to host immune defense against intracellular Acinetobacter baumannii infection. Infect Immun. 2013; 82(3):1112-22. PMC: 3958010. DOI: 10.1128/IAI.01459-13. View

10.

Knapp S, Wieland C, Florquin S, Pantophlet R, Dijkshoorn L, Tshimbalanga N . Differential roles of CD14 and toll-like receptors 4 and 2 in murine Acinetobacter pneumonia. Am J Respir Crit Care Med. 2005; 173(1):122-9. DOI: 10.1164/rccm.200505-730OC. View

11.

Talbot G, Bradley J, Edwards Jr J, Gilbert D, Scheld M, Bartlett J . Bad bugs need drugs: an update on the development pipeline from the Antimicrobial Availability Task Force of the Infectious Diseases Society of America. Clin Infect Dis. 2006; 42(5):657-68. DOI: 10.1086/499819. View

12.

Erridge C, Moncayo-Nieto O, Morgan R, Young M, Poxton I . Acinetobacter baumannii lipopolysaccharides are potent stimulators of human monocyte activation via Toll-like receptor 4 signalling. J Med Microbiol. 2007; 56(Pt 2):165-171. DOI: 10.1099/jmm.0.46823-0. View

13.

Albiger B, Dahlberg S, Sandgren A, Wartha F, Beiter K, Katsuragi H . Toll-like receptor 9 acts at an early stage in host defence against pneumococcal infection. Cell Microbiol. 2006; 9(3):633-44. DOI: 10.1111/j.1462-5822.2006.00814.x. View

14.

Trottier V, Segura P, Namias N, King D, Pizano L, Schulman C . Outcomes of Acinetobacter baumannii infection in critically ill burned patients. J Burn Care Res. 2007; 28(2):248-54. DOI: 10.1097/BCR.0B013E318031A20F. View

15.

Falagas M, Bliziotis I . Pandrug-resistant Gram-negative bacteria: the dawn of the post-antibiotic era?. Int J Antimicrob Agents. 2007; 29(6):630-6. DOI: 10.1016/j.ijantimicag.2006.12.012. View

16.

Bhan U, Lukacs N, Osterholzer J, Newstead M, Zeng X, Moore T . TLR9 is required for protective innate immunity in Gram-negative bacterial pneumonia: role of dendritic cells. J Immunol. 2007; 179(6):3937-46. DOI: 10.4049/jimmunol.179.6.3937. View

17.

van Faassen H, KuoLee R, Harris G, Zhao X, Conlan J, Chen W . Neutrophils play an important role in host resistance to respiratory infection with Acinetobacter baumannii in mice. Infect Immun. 2007; 75(12):5597-608. PMC: 2168347. DOI: 10.1128/IAI.00762-07. View

18.

Barton G . A calculated response: control of inflammation by the innate immune system. J Clin Invest. 2008; 118(2):413-20. PMC: 2214713. DOI: 10.1172/JCI34431. View

19.

Plitas G, Burt B, Nguyen H, Bamboat Z, DeMatteo R . Toll-like receptor 9 inhibition reduces mortality in polymicrobial sepsis. J Exp Med. 2008; 205(6):1277-83. PMC: 2413026. DOI: 10.1084/jem.20080162. View

20.

Bhan U, Trujillo G, Lyn-Kew K, Newstead M, Zeng X, Hogaboam C . Toll-like receptor 9 regulates the lung macrophage phenotype and host immunity in murine pneumonia caused by Legionella pneumophila. Infect Immun. 2008; 76(7):2895-904. PMC: 2446723. DOI: 10.1128/IAI.01489-07. View