Clearance of Pneumococcal Colonization in Infants Is Delayed through Altered Macrophage Trafficking

English version České info

Infants are particularly susceptible to infections, though why is not well understood. One important cause of infant mortality worldwide is infection with Streptococcus pneumoniae, the pneumococcus. All pneumococcal disease begins with asymptomatic colonization of the upper respiratory tract. Infants are also more likely to carry pneumococci, and on average each carriage event has a longer duration. Here, we used an infant mouse model of pneumococcal colonization to study the mechanisms underlying delayed clearance of carriage. We found that infant mice were unable to recruit the effector cells of clearance, macrophages, into the lumen of the upper airway, and that this delay was accompanied by an inability to produce a macrophage chemoattractant in the nasopharynx. We attribute this defect to a dysregulation in the expression of these chemokines and show this effect results from the commensal bacterial flora of infants. Our findings provide an explanation for why infants are more susceptible to being colonized with and infected by pneumococci.

Vyšlo v časopise: Clearance of Pneumococcal Colonization in Infants Is Delayed through Altered Macrophage Trafficking. PLoS Pathog 11(6): e32767. doi:10.1371/journal.ppat.1005004
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1005004

Souhrn

Zdroje

1. Adkins B (2013) Neonatal immunology: responses to pathogenic microorganisms and epigenetics reveal an “immunodiverse” developmental state. Immunol Res 57: 246–257. doi: 10.1007/s12026-013-8439-2 24214026

2. O'Brien KL, Wolfson LJ, Watt JP, Henkle E, Deloria-Knoll M, et al. (2009) Burden of disease caused by Streptococcus pneumoniae in children younger than 5 years: global estimates. Lancet 374: 893–902. doi: 10.1016/S0140-6736(09)61204-6 19748398

3. Gray BM, Converse GM, Dillon HC (1980) Epidemiologic studies of Streptococcus pneumoniae in infants: acquisition, carriage, and infection during the first 24 months of life. J Infect Dis 142: 923–933. 7462701

4. Bogaert D, De Groot R, Hermans PWM (2004) Streptococcus pneumoniae colonisation: the key to pneumococcal disease. Lancet Infect Dis 4: 144–154. doi: 10.1016/S1473-3099(04)00938-7 14998500

5. Weiser JN (2009) The pneumococcus: why a commensal misbehaves. J Mol Med 88: 97–102. doi: 10.1007/s00109-009-0557-x 19898768

6. Levine H, Zarka S, Dagan R, Sela T, Rozhavski V, et al. (2012) Transmission of Streptococcus pneumoniae in adults may occur through saliva. Epidemiol Infect 140: 561–565. doi: 10.1017/S0950268811000884 21676361

7. McCool TL, Cate TR, Moy G, Weiser JN (2002) The immune response to pneumococcal proteins during experimental human carriage. J Exp Med 195: 359–365. 11828011

8. Sleeman KL, Griffiths D, Shackley F, Diggle L, Gupta S, et al. (2006) Capsular serotype-specific attack rates and duration of carriage of Streptococcus pneumoniae in a population of children. J Infect Dis 194: 682–688. doi: 10.1086/505710 16897668

9. Bogaert D, van Belkum A, Sluijter M, Luijendijk A, De Groot R, et al. (2004) Colonisation by Streptococcus pneumoniae and Staphylococcus aureus in healthy children. Lancet 363: 1871–1872. doi: 10.1016/S0140-6736(04)16357-5 15183627

10. Turner P, Turner C, Jankhot A, Helen N, Lee SJ, et al. (2012) A longitudinal study of Streptococcus pneumoniae carriage in a cohort of infants and their mothers on the Thailand-Myanmar border. PLoS ONE 7: e38271. doi: 10.1371/journal.pone.0038271 22693610

11. Darboe MK, Fulford AJ, Secka O, Prentice AM (2010) The dynamics of nasopharyngeal Streptococcus pneumoniae carriage among rural Gambian mother-infant pairs. BMC Infect Dis 10: 195. doi: 10.1186/1471-2334-10-195 20602782

12. Högberg L, Geli P, Ringberg H, Melander E, Lipsitch M, et al. (2007) Age- and serogroup-related differences in observed durations of nasopharyngeal carriage of penicillin-resistant pneumococci. J Clin Microbiol 45: 948–952. doi: 10.1128/JCM.01913-06 17202280

13. Lipsitch M, Whitney CG, Zell E, Kaijalainen T, Dagan R, et al. (2005) Are anticapsular antibodies the primary mechanism of protection against invasive pneumococcal disease? PLoS Med 2: e15. doi: 10.1371/journal.pmed.0020015 15696204

14. Kadioglu A, Weiser JN, Paton JC, Andrew PW (2008) The role of Streptococcus pneumoniae virulence factors in host respiratory colonization and disease. Nat Rev Micro 6: 288–301. doi: 10.1038/nrmicro1871

15. McCool TL, Weiser JN (2004) Limited role of antibody in clearance of Streptococcus pneumoniae in a murine model of colonization. Infect Immun 72: 5807–5813. doi: 10.1128/IAI.72.10.5807-5813.2004 15385481

16. van Rossum AMC, Lysenko ES, Weiser JN (2005) Host and bacterial factors contributing to the clearance of colonization by Streptococcus pneumoniae in a murine model. Infect Immun 73: 7718–7726. doi: 10.1128/IAI.73.11.7718-7726.2005 16239576

17. Lu Y-J, Gross J, Bogaert D, Finn A, Bagrade L, et al. (2008) Interleukin-17A mediates acquired immunity to pneumococcal colonization. PLoS Pathog 4: e1000159. doi: 10.1371/journal.ppat.1000159 18802458

18. Zhang Z, Clarke TB, Weiser JN (2009) Cellular effectors mediating Th17-dependent clearance of pneumococcal colonization in mice. J Clin Invest 119: 1899–1909. doi: 10.1172/JCI36731 19509469

19. Davis KM, Nakamura S, Weiser JN (2011) Nod2 sensing of lysozyme-digested peptidoglycan promotes macrophage recruitment and clearance of S. pneumoniae colonization in mice. J Clin Invest 121: 3666–3676. doi: 10.1172/JCI57761 21841315

20. Dorrington MG, Roche AM, Chauvin SE, Tu Z, Mossman KL, et al. (2013) MARCO is required for TLR2- and Nod2-mediated responses to Streptococcus pneumoniae and clearance of pneumococcal colonization in the murine nasopharynx. J Immunol 190: 250–258. doi: 10.4049/jimmunol.1202113 23197261

21. Rutledge BJ, Rayburn H, Rosenberg R, North RJ, Gladue RP, et al. (1995) High level monocyte chemoattractant protein-1 expression in transgenic mice increases their susceptibility to intracellular pathogens. J Immunol 155: 4838–4843. 7594486

22. Siegel SJ, Roche AM, Weiser JN (2014) Influenza promotes pneumococcal growth during coinfection by providing host sialylated substrates as a nutrient source. Cell Host Microbe 16: 55–67. doi: 10.1016/j.chom.2014.06.005 25011108

23. Renz H, Brandtzaeg P, Hornef M (2012) The impact of perinatal immune development on mucosal homeostasis and chronic inflammation. Nat Rev Immunol 12: 9–23. doi: 10.1038/nri3112

24. Deshmukh HS, Liu Y, Menkiti OR, Mei J, Dai N, et al. (2014) The microbiota regulates neutrophil homeostasis and host resistance to Escherichia coli K1 sepsis in neonatal mice. Nat Med 20: 524–530. doi: 10.1038/nm.3542 24747744

25. Bogaert D, Weinberger D, Thompson C, Lipsitch M, Malley R (2009) Impaired innate and adaptive immunity to Streptococcus pneumoniae and its effect on colonization in an infant mouse model. Infect Immun 77: 1613–1622. doi: 10.1128/IAI.00871-08 19168741

26. Krone CL, Trzciński K, Zborowski T, Sanders EAM, Bogaert D (2013) Impaired innate mucosal immunity in aged mice permits prolonged Streptococcus pneumoniae colonization. Infect Immun 81: 4615–4625. doi: 10.1128/IAI.00618-13 24082075

27. Kollmann TR, Levy O, Montgomery RR, Goriely S (2012) Innate immune function by Toll-like receptors: distinct responses in newborns and the elderly. Immunity 37: 771–783. doi: 10.1016/j.immuni.2012.10.014 23159225

28. Stockinger S, Hornef MW, Chassin C (2011) Establishment of intestinal homeostasis during the neonatal period. Cell Mol Life Sci 68: 3699–3712. doi: 10.1007/s00018-011-0831-2 21952827

29. Fulde M, Hornef MW (2014) Maturation of the enteric mucosal innate immune system during the postnatal period. Immunol Rev 260: 21–34. doi: 10.1111/imr.12190 24942679

30. Clarke TB, Davis KM, Lysenko ES, Zhou AY, Yu Y, et al. (2010) Recognition of peptidoglycan from the microbiota by Nod1 enhances systemic innate immunity. Nat Med 16: 228–231. doi: 10.1038/nm.2087 20081863

31. van Benten IJ, van Drunen CM, Koopman LP, van Middelkoop BC, Hop WCJ, et al. (2005) Age- and infection-related maturation of the nasal immune response in 0-2-year-old children. Allergy 60: 226–232. doi: 10.1111/j.1398-9995.2005.00684.x 15647045

32. Dogliotti G, Galliera E, Licastro F, Corsi MM (2010) Age-related changes in plasma levels of BDNF in Down syndrome patients. Immun Ageing 7: 2. doi: 10.1186/1742-4933-7-2 20181009

33. Tsou C- L, Peters W, Si Y, Slaymaker S, Aslanian AM, et al. (2007) Critical roles for CCR2 and MCP-3 in monocyte mobilization from bone marrow and recruitment to inflammatory sites. J Clin Invest 117: 902–909. doi: 10.1172/JCI29919 17364026

34. Jia T, Serbina NV, Brandl K, Zhong MX, Leiner IM, et al. (2008) Additive roles for MCP-1 and MCP-3 in CCR2-mediated recruitment of inflammatory monocytes during Listeria monocytogenes infection. J Immunol 180: 6846–6853. 18453605

35. Serbina NV, Shi C, Pamer EG (2012) Monocyte-mediated immune defense against murine Listeria monocytogenes infection. Adv Immunol 113: 119–134. doi: 10.1016/B978-0-12-394590-7.00003-8 22244581

36. Walker CLF, Rudan I, Liu L, Nair H, Theodoratou E, et al. (2013) Global burden of childhood pneumonia and diarrhoea. Lancet 381: 1405–1416. doi: 10.1016/S0140-6736(13)60222-6 23582727

37. Tettelin H, Nelson KE, Paulsen IT, Eisen JA, Read TD, et al. (2001) Complete genome sequence of a virulent isolate of Streptococcus pneumoniae. Science 293: 498–506. doi: 10.1126/science.1061217 11463916

38. Richard AL, Siegel SJ, Erikson J, Weiser JN (2014) TLR2 Signaling Decreases Transmission of Streptococcus pneumoniae by Limiting Bacterial Shedding in an Infant Mouse Influenza A Co-infection Model. PLoS Pathog 10: e1004339. doi: 10.1371/journal.ppat.1004339 25166617

39. Beisswenger C, Lysenko ES, Weiser JN (2009) Early bacterial colonization induces toll-like receptor-dependent transforming growth factor beta signaling in the epithelium. Infect Immun 77: 2212–2220. doi: 10.1128/IAI.01224-08 19255194

40. Hildebrand DG, Alexander E, Hörber S, Lehle S, Obermayer K, et al. (2013) IκBζ is a transcriptional key regulator of CCL2/MCP-1. J Immunol 190: 4812–4820. doi: 10.4049/jimmunol.1300089 23547114

41. Wang X, Seed B (2003) A PCR primer bank for quantitative gene expression analysis. Nucleic Acids Res 31: e154. 14654707

42. Fife BT, Huffnagle GB, Kuziel WA, Karpus WJ (2000) CC chemokine receptor 2 is critical for induction of experimental autoimmune encephalomyelitis. J Exp Med 192: 899–905. 10993920

43. Hill DA, Siracusa MC, Abt MC, Kim BS, Kobuley D, et al. (2012) Commensal bacteria-derived signals regulate basophil hematopoiesis and allergic inflammation. Nat Med 18: 538–546. doi: 10.1038/nm.2657 22447074