#PAGE_PARAMS# #ADS_HEAD_SCRIPTS# #MICRODATA#

Subgingival Microbial Communities in Leukocyte Adhesion Deficiency and Their Relationship with Local Immunopathology


Leukocyte adhesion deficiency (LAD) is a primary immunodeficiency resulting from gene mutations in the CD18 subunit of β2 integrins that lead to defective neutrophil adhesion and transmigration into tissues. Affected patients suffer from recurrent life threatening infections and from a severe form of the oral disease periodontitis. The setting of this rare monogenic immune disorder provides a unique opportunity to explore consequences of defective neutrophil tissue transmigration on immunity and microbial colonization in barrier sites such as the oral mucosa. Furthermore, characterization of the oral- subgingival microbiome in LAD expands our understanding of LAD periodontitis, an aggressive disease which is recalcitrant to treatment and often leads to loss of the entire dentition in adolescence. Our current studies in a cohort of LAD patients show that the subgingival microbiome in LAD- periodontitis is unique in its composition and differs from that of health and aggressive periodontitis. Notably our studies reveal that the subgingival communities of LAD can serve as initial triggers for local immunopathology through translocation of bacterial products into tissues and stimulation of local IL-23-related destructive inflammatory responses.


Vyšlo v časopise: Subgingival Microbial Communities in Leukocyte Adhesion Deficiency and Their Relationship with Local Immunopathology. PLoS Pathog 11(3): e32767. doi:10.1371/journal.ppat.1004698
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004698

Souhrn

Leukocyte adhesion deficiency (LAD) is a primary immunodeficiency resulting from gene mutations in the CD18 subunit of β2 integrins that lead to defective neutrophil adhesion and transmigration into tissues. Affected patients suffer from recurrent life threatening infections and from a severe form of the oral disease periodontitis. The setting of this rare monogenic immune disorder provides a unique opportunity to explore consequences of defective neutrophil tissue transmigration on immunity and microbial colonization in barrier sites such as the oral mucosa. Furthermore, characterization of the oral- subgingival microbiome in LAD expands our understanding of LAD periodontitis, an aggressive disease which is recalcitrant to treatment and often leads to loss of the entire dentition in adolescence. Our current studies in a cohort of LAD patients show that the subgingival microbiome in LAD- periodontitis is unique in its composition and differs from that of health and aggressive periodontitis. Notably our studies reveal that the subgingival communities of LAD can serve as initial triggers for local immunopathology through translocation of bacterial products into tissues and stimulation of local IL-23-related destructive inflammatory responses.


Zdroje

1. Rosenzweig SD, Holland SM (2004) Phagocyte immunodeficiencies and their infections. J Allergy Clin Immunol 113: 620–626. 15100664

2. Hanna S, Etzioni A (2011) New host defense mechanisms against Candida species clarify the basis of clinical phenotypes. J Allergy Clin Immunol 127: 1433–1437. doi: 10.1016/j.jaci.2011.03.026 21497889

3. Gerald L. Mandell JEB, and Raphael Dolin (2009) Mandell, Douglas, and Bennett’s Principles and Practice of Infectious Diseases In: Gerald L. Mandell JEB, and Raphael Dolin, editor. Mandell, Douglas, and Bennett’s Principles and Practice of Infectious Diseases Philadelphia: Elsevier. doi: 10.1056/NEJMoa1304839.Two 24450891

4. Uzel G, Tng E, Rosenzweig SD, Hsu AP, Shaw JM, et al. (2008) Reversion mutations in patients with leukocyte adhesion deficiency type-1 (LAD-1). Blood 111: 209–218. 17875809

5. Hanna S, Etzioni A (2012) Leukocyte adhesion deficiencies. Ann N Y Acad Sci 1250: 50–55. doi: 10.1111/j.1749-6632.2011.06389.x 22276660

6. Moutsopoulos N (2014) Defective neutrophil recruitment in leukocyte adhesion deficiency causes local IL-17–driven inflammatory bone loss. Science Translational Medicine 6: 40.

7. Hajishengallis E, Hajishengallis G (2014) Neutrophil homeostasis and periodontal health in children and adults. J Dent Res 93: 231–237. doi: 10.1177/0022034513507956 24097856

8. Armitage GC (1999) Development of a classification system for periodontal diseases and conditions. Ann Periodontol 4: 1–6. 10863370

9. Abusleme L, Dupuy AK, Dutzan N, Silva N, Burleson JA, et al. (2013) The subgingival microbiome in health and periodontitis and its relationship with community biomass and inflammation. ISME J 7: 1016–1025. doi: 10.1038/ismej.2012.174 23303375

10. Reig M, Baquero F, Garcia-Campello M, Loza E (1985) Leptotrichia buccalis bacteremia in neutropenic children. J Clin Microbiol 22: 320–321. 4031045

11. Tanner AC, Mathney JM, Kent RL, Chalmers NI, Hughes CV, et al. (2011) Cultivable anaerobic microbiota of severe early childhood caries. J Clin Microbiol 49: 1464–1474. doi: 10.1128/JCM.02427-10 21289150

12. Hajishengallis G (2014) Immunomicrobial pathogenesis of periodontitis: keystones, pathobionts, and host response. Trends Immunol 35: 3–11. doi: 10.1016/j.it.2013.09.001 24269668

13. Socransky SS, Haffajee AD, Cugini MA, Smith C, Kent RL Jr. (1998) Microbial complexes in subgingival plaque. J Clin Periodontol 25: 134–144. 9495612

14. Colombo AP, Boches SK, Cotton SL, Goodson JM, Kent R, et al. (2009) Comparisons of subgingival microbial profiles of refractory periodontitis, severe periodontitis, and periodontal health using the human oral microbe identification microarray. J Periodontol 80: 1421–1432. doi: 10.1902/jop.2009.090185 19722792

15. Colombo AP, Bennet S, Cotton SL, Goodson JM, Kent R, et al. (2012) Impact of periodontal therapy on the subgingival microbiota of severe periodontitis: comparison between good responders and individuals with refractory periodontitis using the human oral microbe identification microarray. J Periodontol 83: 1279–1287. 22324467

16. Fine DH, Markowitz K, Fairlie K, Tischio-Bereski D, Ferrendiz J, et al. (2013) A consortium of Aggregatibacter actinomycetemcomitans, Streptococcus parasanguinis, and Filifactor alocis is present in sites prior to bone loss in a longitudinal study of localized aggressive periodontitis. J Clin Microbiol 51: 2850–2861. doi: 10.1128/JCM.00729-13 23784124

17. Fine DH, Markowitz K, Furgang D, Fairlie K, Ferrandiz J, et al. (2007) Aggregatibacter actinomycetemcomitans and its relationship to initiation of localized aggressive periodontitis: longitudinal cohort study of initially healthy adolescents. J Clin Microbiol 45: 3859–3869. 17942658

18. Nares S, Moutsopoulos NM, Angelov N, Rangel ZG, Munson PJ, et al. (2009) Rapid myeloid cell transcriptional and proteomic responses to periodontopathogenic Porphyromonas gingivalis. Am J Pathol 174: 1400–1414. doi: 10.2353/ajpath.2009.080677 19264901

19. Hasturk H, Kantarci A, Van Dyke TE (2012) Oral inflammatory diseases and systemic inflammation: role of the macrophage. Front Immunol 3: 118. doi: 10.3389/fimmu.2012.00118 22623923

20. Cox DP, Weathers DR (2008) Leukocyte adhesion deficiency type 1: an important consideration in the clinical differential diagnosis of prepubertal periodontitis. A case report and review of the literature. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 105: 86–90. 17618138

21. Hajishengallis G (2014) The inflammophilic character of the periodontitis-associated microbiota. Mol Oral Microbiol.

22. Socransky SS, Haffajee AD (2005) Periodontal microbial ecology. Periodontol 2000 38: 135–187.

23. Littman DR, Pamer EG (2011) Role of the commensal microbiota in normal and pathogenic host immune responses. Cell Host Microbe 10: 311–323. doi: 10.1016/j.chom.2011.10.004 22018232

24. Fukuda S, Toh H, Hase K, Oshima K, Nakanishi Y, et al. (2011) Bifidobacteria can protect from enteropathogenic infection through production of acetate. Nature 469: 543–547. doi: 10.1038/nature09646 21270894

25. Ivanov II, Atarashi K, Manel N, Brodie EL, Shima T, et al. (2009) Induction of intestinal Th17 cells by segmented filamentous bacteria. Cell 139: 485–498. doi: 10.1016/j.cell.2009.09.033 19836068

26. Atarashi K, Tanoue T, Shima T, Imaoka A, Kuwahara T, et al. (2011) Induction of colonic regulatory T cells by indigenous Clostridium species. Science 331: 337–341. doi: 10.1126/science.1198469 21205640

27. Darveau RP (2010) Periodontitis: a polymicrobial disruption of host homeostasis. Nat Rev Microbiol 8: 481–490. doi: 10.1038/nrmicro2337 20514045

28. Shaddox LM, Huang H, Lin T, Hou W, Harrison PL, et al. (2012) Microbiological characterization in children with aggressive periodontitis. J Dent Res 91: 927–933. 22863892

29. Jorth P, Turner KH, Gumus P, Nizam N, Buduneli N, et al. (2014) Metatranscriptomics of the human oral microbiome during health and disease. MBio 5: e01012–01014. doi: 10.1128/mBio.01012-14 24692635

30. Davies D (2003) Understanding biofilm resistance to antibacterial agents. Nat Rev Drug Discov 2: 114–122. 12563302

31. Elinav E, Strowig T, Kau AL, Henao-Mejia J, Thaiss CA, et al. (2011) NLRP6 inflammasome regulates colonic microbial ecology and risk for colitis. Cell 145: 745–757. doi: 10.1016/j.cell.2011.04.022 21565393

32. Bloom SM, Bijanki VN, Nava GM, Sun L, Malvin NP, et al. (2011) Commensal Bacteroides species induce colitis in host-genotype-specific fashion in a mouse model of inflammatory bowel disease. Cell Host Microbe 9: 390–403. doi: 10.1016/j.chom.2011.04.009 21575910

33. Roberts MW, Atkinson JC (1990) Oral manifestations associated with leukocyte adhesion deficiency: a five-year case study. Pediatr Dent 12: 107–111. 2133935

34. Majorana A, Notarangelo LD, Savoldi E, Gastaldi G, Lozada-Nur F (1999) Leukocyte adhesion deficiency in a child with severe oral involvement. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 87: 691–694. 10397659

35. Lyczak JB, Cannon CL, Pier GB (2000) Establishment of Pseudomonas aeruginosa infection: lessons from a versatile opportunist. Microbes Infect 2: 1051–1060. 10967285

36. Harmsen M, Yang L, Pamp SJ, Tolker-Nielsen T (2010) An update on Pseudomonas aeruginosa biofilm formation, tolerance, and dispersal. FEMS Immunol Med Microbiol 59: 253–268. doi: 10.1111/j.1574-695X.2010.00690.x 20497222

37. Mellouli F, Ksouri H, Barbouche R, Maamer M, Hamed LB, et al. (2010) Successful treatment of Fusarium solani ecthyma gangrenosum in a patient affected by leukocyte adhesion deficiency type 1 with granulocytes transfusions. BMC Dermatol 10: 10. doi: 10.1186/1471-5945-10-10 20929531

38. Dubin PJ, Kolls JK (2007) IL-23 mediates inflammatory responses to mucoid Pseudomonas aeruginosa lung infection in mice. Am J Physiol Lung Cell Mol Physiol 292: L519–528. 17071720

39. McAllister F, Henry A, Kreindler JL, Dubin PJ, Ulrich L, et al. (2005) Role of IL-17A, IL-17F, and the IL-17 receptor in regulating growth-related oncogene-alpha and granulocyte colony-stimulating factor in bronchial epithelium: implications for airway inflammation in cystic fibrosis. J Immunol 175: 404–412. 15972674

40. Couturier MR, Slechta ES, Goulston C, Fisher MA, Hanson KE (2012) Leptotrichia bacteremia in patients receiving high-dose chemotherapy. J Clin Microbiol 50: 1228–1232. doi: 10.1128/JCM.05926-11 22205794

41. Brenchley JM, Price DA, Schacker TW, Asher TE, Silvestri G, et al. (2006) Microbial translocation is a cause of systemic immune activation in chronic HIV infection. Nat Med 12: 1365–1371. 17115046

42. Kristoff J, Haret-Richter G, Ma D, Ribeiro RM, Xu C, et al. (2014) Early microbial translocation blockade reduces SIV-mediated inflammation and viral replication. J Clin Invest 124: 2802–2806. doi: 10.1172/JCI75090 24837437

43. Stark MA, Huo Y, Burcin TL, Morris MA, Olson TS, et al. (2005) Phagocytosis of apoptotic neutrophils regulates granulopoiesis via IL-23 and IL-17. Immunity 22: 285–294. 15780986

44. (2000) Parameter on comprehensive periodontal examination. American Academy of Periodontology. J Periodontol 71: 847–848. 10875687

45. Taylor RD (1966) Modification of the Brown and Brenn gram stain for the differential staining of gram-positive and gram-negative bacteria in tissue sections. Am J Clin Pathol 46: 472–474. 4162586

46. Estes JD, Harris LD, Klatt NR, Tabb B, Pittaluga S, et al. (2010) Damaged intestinal epithelial integrity linked to microbial translocation in pathogenic simian immunodeficiency virus infections. PLoS Pathog 6: e1001052. doi: 10.1371/journal.ppat.1001052 20808901

47. Moutsopoulos NM, Kling HM, Angelov N, Jin W, Palmer RJ, et al. (2012) Porphyromonas gingivalis promotes Th17 inducing pathways in chronic periodontitis. J Autoimmun 39: 294–303. doi: 10.1016/j.jaut.2012.03.003 22560973

Štítky
Hygiena a epidemiológia Infekčné lekárstvo Laboratórium

Článok vyšiel v časopise

PLOS Pathogens


2015 Číslo 3
Najčítanejšie tento týždeň
Najčítanejšie v tomto čísle
Kurzy

Zvýšte si kvalifikáciu online z pohodlia domova

Aktuální možnosti diagnostiky a léčby litiáz
nový kurz
Autori: MUDr. Tomáš Ürge, PhD.

Všetky kurzy
Prihlásenie
Zabudnuté heslo

Zadajte e-mailovú adresu, s ktorou ste vytvárali účet. Budú Vám na ňu zasielané informácie k nastaveniu nového hesla.

Prihlásenie

Nemáte účet?  Registrujte sa

#ADS_BOTTOM_SCRIPTS#