Macrophages Subvert Adaptive Immunity to Urinary Tract Infection

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Urinary tract infection is a common infection with a high propensity for recurrence. The majority of infections are caused by uropathogenic E. coli, a growing public health concern with increasing prevalence of antibiotic resistant strains. Finding therapeutic options that circumvent the need for antibiotics, while boosting patients’ immune response to infection is desirable to counteract further increases in antibiotic resistance and to provide long-lasting resistance to infection. Currently, little is known about how adaptive immune responses, which typically prevent recurrent infection in other organs, arise from the bladder during urinary tract infection. Here, we investigated the initial interactions between immune cell populations of the bladder and uropathogenic E. coli, finding that macrophages are the principal cell population to engulf bacteria. Interestingly, these same cells appear to inhibit the development of adaptive immunity to the bacteria, as their depletion, prior to primary infection, results in a stronger immune response during bacterial challenge. We found that in the absence of macrophages, dendritic cells, which are the most potent initiators of adaptive immunity, are able to take up more bacteria for presentation. Our study has revealed a mechanism in which specific immune cells may act in a manner detrimental to host immunity.

Vyšlo v časopise: Macrophages Subvert Adaptive Immunity to Urinary Tract Infection. PLoS Pathog 11(7): e32767. doi:10.1371/journal.ppat.1005044
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1005044

Souhrn

Zdroje

1. Foxman B (2010) The epidemiology of urinary tract infection. Nature reviews Urology 7: 653–660. doi: 10.1038/nrurol.2010.190 21139641

2. Russo TA, Johnson JR (2003) Medical and economic impact of extraintestinal infections due to Escherichia coli: focus on an increasingly important endemic problem. Microbes Infect 5: 449–456. 12738001

3. Johnson CC (1991) Definitions, classification, and clinical presentation of urinary tract infections. Med Clin North Am 75: 241–252. 1996031

4. Anderson GG, Dodson KW, Hooton TM, Hultgren SJ (2004) Intracellular bacterial communities of uropathogenic Escherichia coli in urinary tract pathogenesis. Trends Microbiol 12: 424–430. 15337164

5. Mysorekar IU, Hultgren SJ (2006) Mechanisms of uropathogenic Escherichia coli persistence and eradication from the urinary tract. Proc Natl Acad Sci U S A 103: 14170–14175. 16968784

6. Chen SL, Wu M, Henderson JP, Hooton TM, Hibbing ME, et al. (2013) Genomic diversity and fitness of E. coli strains recovered from the intestinal and urinary tracts of women with recurrent urinary tract infection. Sci Transl Med 5: 184ra160.

7. Chan CY, St John AL, Abraham SN (2013) Mast cell interleukin-10 drives localized tolerance in chronic bladder infection. Immunity 38: 349–359. doi: 10.1016/j.immuni.2012.10.019 23415912

8. Engel DR, Maurer J, Tittel AP, Weisheit C, Cavlar T, et al. (2008) CCR2 mediates homeostatic and inflammatory release of Gr1(high) monocytes from the bone marrow, but is dispensable for bladder infiltration in bacterial urinary tract infection. J Immunol 181: 5579–5586. 18832716

9. Godaly G, Hang L, Frendeus B, Svanborg C (2000) Transepithelial neutrophil migration is CXCR1 dependent in vitro and is defective in IL-8 receptor knockout mice. J Immunol 165: 5287–5294. 11046063

10. Haraoka M, Hang L, Frendeus B, Godaly G, Burdick M, et al. (1999) Neutrophil recruitment and resistance to urinary tract infection. J Infect Dis 180: 1220–1229. 10479151

11. Ingersoll MA, Kline KA, Nielsen HV, Hultgren SJ (2008) G-CSF induction early in uropathogenic Escherichia coli infection of the urinary tract modulates host immunity. Cell Microbiol 10: 2568–2578. doi: 10.1111/j.1462-5822.2008.01230.x 18754853

12. Shahin RD, Engberg I, Hagberg L, Svanborg Eden C (1987) Neutrophil recruitment and bacterial clearance correlated with LPS responsiveness in local gram-negative infection. Journal of immunology 138: 3475–3480.

13. Daley JM, Thomay AA, Connolly MD, Reichner JS, Albina JE (2008) Use of Ly6G-specific monoclonal antibody to deplete neutrophils in mice. J Leukoc Biol 83: 64–70. 17884993

14. Schiwon M, Weisheit C, Franken L, Gutweiler S, Dixit A, et al. (2014) Crosstalk between sentinel and helper macrophages permits neutrophil migration into infected uroepithelium. Cell 156: 456–468. doi: 10.1016/j.cell.2014.01.006 24485454

15. Ingersoll MA, Albert ML (2013) From infection to immunotherapy: host immune responses to bacteria at the bladder mucosa. Mucosal immunology 6: 1041–1053. doi: 10.1038/mi.2013.72 24064671

16. Nielubowicz GR, Mobley HL (2010) Host-pathogen interactions in urinary tract infection. Nat Rev Urol 7: 430–441. doi: 10.1038/nrurol.2010.101 20647992

17. Hopkins WJ, Uehling DT, Balish E (1987) Local and systemic antibody responses accompany spontaneous resolution of experimental cystitis in cynomolgus monkeys. Infect Immun 55: 1951–1956. 3305357

18. Svanborg-Eden C, Svennerholm AM (1978) Secretory immunoglobulin A and G antibodies prevent adhesion of Escherichia coli to human urinary tract epithelial cells. Infection and immunity 22: 790–797. 83303

19. Thumbikat P, Waltenbaugh C, Schaeffer AJ, Klumpp DJ (2006) Antigen-specific responses accelerate bacterial clearance in the bladder. J Immunol 176: 3080–3086. 16493067

20. Hung CS, Dodson KW, Hultgren SJ (2009) A murine model of urinary tract infection. Nat Protoc 4: 1230–1243. doi: 10.1038/nprot.2009.116 19644462

21. Probst HC, Tschannen K, Odermatt B, Schwendener R, Zinkernagel RM, et al. (2005) Histological analysis of CD11c-DTR/GFP mice after in vivo depletion of dendritic cells. Clin Exp Immunol 141: 398–404. 16045728

22. Gardiner RA, Seymour GJ, Lavin MF, Strutton GM, Gemmell E, et al. (1986) Immunohistochemical analysis of the human bladder. Br J Urol 58: 19–25. 2936415

23. Hart DN, Fabre JW (1981) Demonstration and characterization of Ia-positive dendritic cells in the interstitial connective tissues of rat heart and other tissues, but not brain. J Exp Med 154: 347–361. 6943285

24. Hart DN, Fabre JW (1981) Major histocompatibility complex antigens in rat kidney, ureter, and bladder. Localization with monoclonal antibodies and demonstration of Ia-positive dendritic cells. Transplantation 31: 318–325. 6785911

25. Hjelm E, Forsum U, Klareskog L (1982) Anti-Ia-reactive cells in the urinary tract of man, guinea-pig, rat and mouse. Scand J Immunol 16: 531–538. 6818686

26. Gautier EL, Shay T, Miller J, Greter M, Jakubzick C, et al. (2012) Gene-expression profiles and transcriptional regulatory pathways that underlie the identity and diversity of mouse tissue macrophages. Nat Immunol 13: 1118–1128. doi: 10.1038/ni.2419 23023392

27. Tamoutounour S, Henri S, Lelouard H, de Bovis B, de Haar C, et al. (2012) CD64 distinguishes macrophages from dendritic cells in the gut and reveals the Th1-inducing role of mesenteric lymph node macrophages during colitis. European journal of immunology 42: 3150–3166. doi: 10.1002/eji.201242847 22936024

28. Jonsson F, Daeron M (2012) Mast cells and company. Front Immunol 3: 16. doi: 10.3389/fimmu.2012.00016 22566901

29. Jakubzick C, Gautier EL, Gibbings SL, Sojka DK, Schlitzer A, et al. (2013) Minimal differentiation of classical monocytes as they survey steady-state tissues and transport antigen to lymph nodes. Immunity 39: 599–610. doi: 10.1016/j.immuni.2013.08.007 24012416

30. Tamoutounour S, Guilliams M, Montanana Sanchis F, Liu H, Terhorst D, et al. (2013) Origins and functional specialization of macrophages and of conventional and monocyte-derived dendritic cells in mouse skin. Immunity 39: 925–938. doi: 10.1016/j.immuni.2013.10.004 24184057

31. Dyer KD, Garcia-Crespo KE, Killoran KE, Rosenberg HF (2011) Antigen profiles for the quantitative assessment of eosinophils in mouse tissues by flow cytometry. Journal of immunological methods 369: 91–97. doi: 10.1016/j.jim.2011.04.009 21565196

32. Tacke F, Ginhoux F, Jakubzick C, van Rooijen N, Merad M, et al. (2006) Immature monocytes acquire antigens from other cells in the bone marrow and present them to T cells after maturing in the periphery. J Exp Med 203: 583–597. 16492803

33. Serbina NV, Pamer EG (2006) Monocyte emigration from bone marrow during bacterial infection requires signals mediated by chemokine receptor CCR2. Nat Immunol 7: 311–317. 16462739

34. Ingersoll MA, Platt AM, Potteaux S, Randolph GJ (2011) Monocyte trafficking in acute and chronic inflammation. Trends in Immunology 32: 470–477. doi: 10.1016/j.it.2011.05.001 21664185

35. Van Rooijen N, Sanders A (1994) Liposome mediated depletion of macrophages: mechanism of action, preparation of liposomes and applications. J Immunol Methods 174: 83–93. 8083541

36. Hashimoto D, Chow A, Noizat C, Teo P, Beasley MB, et al. (2013) Tissue-resident macrophages self-maintain locally throughout adult life with minimal contribution from circulating monocytes. Immunity 38: 792–804. doi: 10.1016/j.immuni.2013.04.004 23601688

37. Schreiber HA, Loschko J, Karssemeijer RA, Escolano A, Meredith MM, et al. (2013) Intestinal monocytes and macrophages are required for T cell polarization in response to Citrobacter rodentium. J Exp Med 210: 2025–2039. doi: 10.1084/jem.20130903 24043764

38. Silva MT (2010) Neutrophils and macrophages work in concert as inducers and effectors of adaptive immunity against extracellular and intracellular microbial pathogens. J Leukoc Biol 87: 805–813. doi: 10.1189/jlb.1109767 20110444

39. Jakubzick C, Helft J, Kaplan TJ, Randolph GJ (2008) Optimization of methods to study pulmonary dendritic cell migration reveals distinct capacities of DC subsets to acquire soluble versus particulate antigen. J Immunol Methods 337: 121–131. doi: 10.1016/j.jim.2008.07.005 18662693

40. Jakubzick C, Tacke F, Llodra J, van Rooijen N, Randolph GJ (2006) Modulation of dendritic cell trafficking to and from the airways. J Immunol 176: 3578–3584. 16517726

41. Kradin RL, Liu HW, van Rooijen N, Springer K, Zhao LH, et al. (1999) Pulmonary immunity to Listeria is enhanced by elimination of alveolar macrophages. Am J Respir Crit Care Med 159: 1967–1974. 10351946

42. MacLean JA, Xia W, Pinto CE, Zhao L, Liu HW, et al. (1996) Sequestration of inhaled particulate antigens by lung phagocytes. A mechanism for the effective inhibition of pulmonary cell-mediated immunity. Am J Pathol 148: 657–666. 8579128

43. Jakubzick C, Bogunovic M, Bonito AJ, Kuan EL, Merad M, et al. (2008) Lymph-migrating, tissue-derived dendritic cells are minor constituents within steady-state lymph nodes. J Exp Med 205: 2839–2850. doi: 10.1084/jem.20081430 18981237

44. Minagawa S, Ohyama C, Hatakeyama S, Tsuchiya N, Kato T, et al. (2005) Activation of natural killer T cells by alpha-galactosylceramide mediates clearance of bacteria in murine urinary tract infection. J Urol 173: 2171–2174. 15879881

45. Anderson GG, Palermo JJ, Schilling JD, Roth R, Heuser J, et al. (2003) Intracellular bacterial biofilm-like pods in urinary tract infections. Science 301: 105–107. 12843396

46. Mulvey MA, Schilling JD, Hultgren SJ (2001) Establishment of a persistent Escherichia coli reservoir during the acute phase of a bladder infection. Infection and immunity 69: 4572–4579. 11402001

47. Petty NK, Ben Zakour NL, Stanton-Cook M, Skippington E, Totsika M, et al. (2014) Global dissemination of a multidrug resistant Escherichia coli clone. Proc Natl Acad Sci U S A 111: 5694–5699. doi: 10.1073/pnas.1322678111 24706808

48. Chaveroche MK, Ghigo JM, d'Enfert C (2000) A rapid method for efficient gene replacement in the filamentous fungus Aspergillus nidulans. Nucleic Acids Res 28: E97. 11071951

49. De Boer WI, Rebel JM, Foekens JA, Vermey M, Van der Kwast TH (1993) Characterization of mouse urothelial cell lines in different phases of transitional-cell carcinogenesis. Int J Cancer 54: 1022–1027. 7687588