Skip to main content
PMC home page
Infection and Immunity logoLink to Infection and Immunity
. 1997 Feb;65(2):739–749. doi: 10.1128/iai.65.2.739-749.1997

In situ characterization of inflammatory responses in the rectal mucosae of patients with shigellosis.

D Islam 1, B Veress 1, P K Bardhan 1, A A Lindberg 1, B Christensson 1
PMCID: PMC176120  PMID: 9009337

Abstract

Shigella species cause bacillary dysentery in humans by invading epithelial cells of the colonic mucosa leading to colonic epithelial cell destruction and inflammation. For further analysis of local gut inflammation, morphological changes and the potential involvement of mediators in regulatory mechanisms of cell activation and cell proliferation were studied immunohistochemically in rectal mucosal biopsies taken from patients during the acute phase of shigellosis and at convalescence. Rectal biopsies from 25 Shigella dysenteriae-1 and 10 Shigella flexneri-infected patients and from 40 controls were studied. The frequencies of proliferative cells (Ki67-positive cells), p53-immunostaining cells, and cells coexpressing Ki67 with CD3 or with p53 were analyzed. Immunostaining for the inducible nitric oxide synthase (iNOS) and the endothelial NOS was assessed. In addition, the frequencies of apoptotic cells and CD68+ cells that engulf apoptotic cells were assessed. By morphological grading, 20% of the patients had advanced inflammation (grade 3) in the acute phase; mild inflammation (grade 1) was seen in 37% of the patients at convalescence as well as in 10% of the controls. The findings in the present study suggest that in the acute phase of shigellosis inflammation is characterized by increased cell turnover in the lamina propria (LP) and the epithelium, increased iNOS expression in the surface epithelium, and apoptosis, which seems to be associated with LP macrophages. The findings also suggest that neither p53 nor iNOS are important factors for the induction of apoptosis in shigellosis. Expression of p53 may be related to early cell activation in crypt epithelium. Moreover, there is an indication of an active, low-level inflammatory process at convalescence. The results thus indicate that Shigella-induced inflammation is associated with a complex series of cellular reactions in the rectal gut mucosa which persist long after clinical symptoms have resolved.

Full Text

The Full Text of this article is available as a PDF (709.6 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Anand B. S., Malhotra V., Bhattacharya S. K., Datta P., Datta D., Sen D., Bhattacharya M. K., Mukherjee P. P., Pal S. C. Rectal histology in acute bacillary dysentery. Gastroenterology. 1986 Mar;90(3):654–660. doi: 10.1016/0016-5085(86)91120-0. [DOI] [PubMed] [Google Scholar]
  2. Apel R., Cohen Z., Andrews C. W., Jr, McLeod R., Steinhart H., Odze R. D. Prospective evaluation of early morphological changes in pelvic ileal pouches. Gastroenterology. 1994 Aug;107(2):435–443. doi: 10.1016/0016-5085(94)90169-4. [DOI] [PubMed] [Google Scholar]
  3. Butler T., Dunn D., Dahms B., Islam M. Causes of death and the histopathologic findings in fatal shigellosis. Pediatr Infect Dis J. 1989 Nov;8(11):767–772. doi: 10.1097/00006454-198911000-00008. [DOI] [PubMed] [Google Scholar]
  4. Bártek J., Bártková J., Vojtesek B., Stasková Z., Lukás J., Rejthar A., Kovarík J., Midgley C. A., Gannon J. V., Lane D. P. Aberrant expression of the p53 oncoprotein is a common feature of a wide spectrum of human malignancies. Oncogene. 1991 Sep;6(9):1699–1703. [PubMed] [Google Scholar]
  5. Duke R. C., Chervenak R., Cohen J. J. Endogenous endonuclease-induced DNA fragmentation: an early event in cell-mediated cytolysis. Proc Natl Acad Sci U S A. 1983 Oct;80(20):6361–6365. doi: 10.1073/pnas.80.20.6361. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Fléjou J. F., Paraf F., Muzeau F., Fékété F., Hénin D., Jothy S., Potet F. Expression of c-erbB-2 oncogene product in Barrett's adenocarcinoma: pathological and prognostic correlations. J Clin Pathol. 1994 Jan;47(1):23–26. doi: 10.1136/jcp.47.1.23. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Gold R., Schmied M., Giegerich G., Breitschopf H., Hartung H. P., Toyka K. V., Lassmann H. Differentiation between cellular apoptosis and necrosis by the combined use of in situ tailing and nick translation techniques. Lab Invest. 1994 Aug;71(2):219–225. [PubMed] [Google Scholar]
  8. Gordon S., Clarke S., Greaves D., Doyle A. Molecular immunobiology of macrophages: recent progress. Curr Opin Immunol. 1995 Feb;7(1):24–33. doi: 10.1016/0952-7915(95)80025-5. [DOI] [PubMed] [Google Scholar]
  9. Haapasalo H., Isola J., Sallinen P., Kalimo H., Helin H., Rantala I. Aberrant p53 expression in astrocytic neoplasms of the brain: association with proliferation. Am J Pathol. 1993 May;142(5):1347–1351. [PMC free article] [PubMed] [Google Scholar]
  10. Haslett C., Savill J. S., Whyte M. K., Stern M., Dransfield I., Meagher L. C. Granulocyte apoptosis and the control of inflammation. Philos Trans R Soc Lond B Biol Sci. 1994 Aug 30;345(1313):327–333. doi: 10.1098/rstb.1994.0113. [DOI] [PubMed] [Google Scholar]
  11. High N., Mounier J., Prévost M. C., Sansonetti P. J. IpaB of Shigella flexneri causes entry into epithelial cells and escape from the phagocytic vacuole. EMBO J. 1992 May;11(5):1991–1999. doi: 10.1002/j.1460-2075.1992.tb05253.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Islam D., Lindberg A. A. Detection of Shigella dysenteriae type 1 and Shigella flexneri in feces by immunomagnetic isolation and polymerase chain reaction. J Clin Microbiol. 1992 Nov;30(11):2801–2806. doi: 10.1128/jcm.30.11.2801-2806.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Islam D., Wretlind B., Hammarström L., Christensson B., Lindberg A. A. Semiquantitative estimation of Shigella antigen-specific antibodies: correlation with disease severity during shigellosis. APMIS. 1996 Jul-Aug;104(7-8):563–574. doi: 10.1111/j.1699-0463.1996.tb04912.x. [DOI] [PubMed] [Google Scholar]
  14. Islam D., Wretlind B., Ryd M., Lindberg A. A., Christensson B. Immunoglobulin subclass distribution and dynamics of Shigella-specific antibody responses in serum and stool samples in shigellosis. Infect Immun. 1995 May;63(5):2054–2061. doi: 10.1128/iai.63.5.2054-2061.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Islam M. M., Azad A. K., Bardhan P. K., Raqib R., Islam D. Pathology of shigellosis and its complications. Histopathology. 1994 Jan;24(1):65–71. doi: 10.1111/j.1365-2559.1994.tb01272.x. [DOI] [PubMed] [Google Scholar]
  16. Isola J., Visakorpi T., Holli K., Kallioniemi O. P. Association of overexpression of tumor suppressor protein p53 with rapid cell proliferation and poor prognosis in node-negative breast cancer patients. J Natl Cancer Inst. 1992 Jul 15;84(14):1109–1114. doi: 10.1093/jnci/84.14.1109. [DOI] [PubMed] [Google Scholar]
  17. Jenkins J. R., Rudge K., Currie G. A. Cellular immortalization by a cDNA clone encoding the transformation-associated phosphoprotein p53. Nature. 1984 Dec 13;312(5995):651–654. doi: 10.1038/312651a0. [DOI] [PubMed] [Google Scholar]
  18. Katakura S., Reinholt F. P., Kärnell A., Huan P. T., Trach D. D., Lindberg A. A. The pathology of Shigella flexneri infection in rhesus monkeys: an endoscopic and histopathological study of colonic lesions. APMIS. 1990 Apr;98(4):313–319. doi: 10.1111/j.1699-0463.1990.tb01038.x. [DOI] [PubMed] [Google Scholar]
  19. Kingsley G., Panayi G. Antigenic responses in reactive arthritis. Rheum Dis Clin North Am. 1992 Feb;18(1):49–66. [PubMed] [Google Scholar]
  20. Kitajima I., Kawahara K., Nakajima T., Soejima Y., Matsuyama T., Maruyama I. Nitric oxide-mediated apoptosis in murine mastocytoma. Biochem Biophys Res Commun. 1994 Oct 14;204(1):244–251. doi: 10.1006/bbrc.1994.2451. [DOI] [PubMed] [Google Scholar]
  21. Levine A. J. The p53 protein and its interactions with the oncogene products of the small DNA tumor viruses. Virology. 1990 Aug;177(2):419–426. doi: 10.1016/0042-6822(90)90505-l. [DOI] [PubMed] [Google Scholar]
  22. Lorsbach R. B., Murphy W. J., Lowenstein C. J., Snyder S. H., Russell S. W. Expression of the nitric oxide synthase gene in mouse macrophages activated for tumor cell killing. Molecular basis for the synergy between interferon-gamma and lipopolysaccharide. J Biol Chem. 1993 Jan 25;268(3):1908–1913. [PubMed] [Google Scholar]
  23. Lundberg J. O., Farkas-Szallasi T., Weitzberg E., Rinder J., Lidholm J., Anggåard A., Hökfelt T., Lundberg J. M., Alving K. High nitric oxide production in human paranasal sinuses. Nat Med. 1995 Apr;1(4):370–373. doi: 10.1038/nm0495-370. [DOI] [PubMed] [Google Scholar]
  24. Martikainen P., Kyprianou N., Tucker R. W., Isaacs J. T. Programmed death of nonproliferating androgen-independent prostatic cancer cells. Cancer Res. 1991 Sep 1;51(17):4693–4700. [PubMed] [Google Scholar]
  25. Mathan M. M., Mathan V. I. Morphology of rectal mucosa of patients with shigellosis. Rev Infect Dis. 1991 Mar-Apr;13 (Suppl 4):S314–S318. doi: 10.1093/clinids/13.supplement_4.s314. [DOI] [PubMed] [Google Scholar]
  26. Mathan M. M., Mathan V. I. Rectal mucosal morphologic abnormalities in normal subjects in southern India: a tropical colonopathy? Gut. 1985 Jul;26(7):710–717. doi: 10.1136/gut.26.7.710. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Mathan M. M., Mathan V. I. Ultrastructural pathology of the rectal mucosa in Shigella dysentery. Am J Pathol. 1986 Apr;123(1):25–38. [PMC free article] [PubMed] [Google Scholar]
  28. Matter A. Microcinematographic and electron microscopic analysis of target cell lysis induced by cytotoxic T lymphocytes. Immunology. 1979 Feb;36(2):179–190. [PMC free article] [PubMed] [Google Scholar]
  29. Messmer U. K., Ankarcrona M., Nicotera P., Brüne B. p53 expression in nitric oxide-induced apoptosis. FEBS Lett. 1994 Nov 21;355(1):23–26. doi: 10.1016/0014-5793(94)01161-3. [DOI] [PubMed] [Google Scholar]
  30. Messmer U. K., Lapetina E. G., Brüne B. Nitric oxide-induced apoptosis in RAW 264.7 macrophages is antagonized by protein kinase C- and protein kinase A-activating compounds. Mol Pharmacol. 1995 Apr;47(4):757–765. [PubMed] [Google Scholar]
  31. Moncada S., Palmer R. M., Higgs E. A. Nitric oxide: physiology, pathophysiology, and pharmacology. Pharmacol Rev. 1991 Jun;43(2):109–142. [PubMed] [Google Scholar]
  32. Ménard R., Sansonetti P. J., Parsot C. Nonpolar mutagenesis of the ipa genes defines IpaB, IpaC, and IpaD as effectors of Shigella flexneri entry into epithelial cells. J Bacteriol. 1993 Sep;175(18):5899–5906. doi: 10.1128/jb.175.18.5899-5906.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Nagao T., Kondo F., Sato T., Nagato Y., Kondo Y. Immunohistochemical detection of aberrant p53 expression in hepatocellular carcinoma: correlation with cell proliferative activity indices, including mitotic index and MIB-1 immunostaining. Hum Pathol. 1995 Mar;26(3):326–333. doi: 10.1016/0046-8177(95)90066-7. [DOI] [PubMed] [Google Scholar]
  34. Nathan C. Nitric oxide as a secretory product of mammalian cells. FASEB J. 1992 Sep;6(12):3051–3064. [PubMed] [Google Scholar]
  35. Nathan C., Xie Q. W. Regulation of biosynthesis of nitric oxide. J Biol Chem. 1994 May 13;269(19):13725–13728. [PubMed] [Google Scholar]
  36. Nussler A. K., Di Silvio M., Billiar T. R., Hoffman R. A., Geller D. A., Selby R., Madariaga J., Simmons R. L. Stimulation of the nitric oxide synthase pathway in human hepatocytes by cytokines and endotoxin. J Exp Med. 1992 Jul 1;176(1):261–264. doi: 10.1084/jem.176.1.261. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Oliner J. D., Kinzler K. W., Meltzer P. S., George D. L., Vogelstein B. Amplification of a gene encoding a p53-associated protein in human sarcomas. Nature. 1992 Jul 2;358(6381):80–83. doi: 10.1038/358080a0. [DOI] [PubMed] [Google Scholar]
  38. Pich A., Chiusa L., Comino A., Navone R. Cell proliferation indices, morphometry and DNA flow cytometry provide objective criteria for distinguishing low and high grade bladder carcinomas. Virchows Arch. 1994;424(2):143–148. doi: 10.1007/BF00193493. [DOI] [PubMed] [Google Scholar]
  39. Rabinovitch A., Suarez-Pinzon W. L., Strynadka K., Schulz R., Lakey J. R., Warnock G. L., Rajotte R. V. Human pancreatic islet beta-cell destruction by cytokines is independent of nitric oxide production. J Clin Endocrinol Metab. 1994 Oct;79(4):1058–1062. doi: 10.1210/jcem.79.4.7962274. [DOI] [PubMed] [Google Scholar]
  40. Raqib R., Lindberg A. A., Björk L., Bardhan P. K., Wretlind B., Andersson U., Andersson J. Down-regulation of gamma interferon, tumor necrosis factor type I, interleukin 1 (IL-1) type I, IL-3, IL-4, and transforming growth factor beta type I receptors at the local site during the acute phase of Shigella infection. Infect Immun. 1995 Aug;63(8):3079–3087. doi: 10.1128/iai.63.8.3079-3087.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Raqib R., Lindberg A. A., Wretlind B., Bardhan P. K., Andersson U., Andersson J. Persistence of local cytokine production in shigellosis in acute and convalescent stages. Infect Immun. 1995 Jan;63(1):289–296. doi: 10.1128/iai.63.1.289-296.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Raqib R., Ljungdahl A., Lindberg A. A., Andersson U., Andersson J. Local entrapment of interferon gamma in the recovery from Shigella dysenteriae type 1 infection. Gut. 1996 Mar;38(3):328–336. doi: 10.1136/gut.38.3.328. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Raqib R., Wretlind B., Andersson J., Lindberg A. A. Cytokine secretion in acute shigellosis is correlated to disease activity and directed more to stool than to plasma. J Infect Dis. 1995 Feb;171(2):376–384. doi: 10.1093/infdis/171.2.376. [DOI] [PubMed] [Google Scholar]
  44. Reinholt F. P., Veress B., Lindquist K., Liljeqvist L. Qualitative assessment and morphometry in the study of the ileal reservoir after restorative proctocolectomy. APMIS. 1989 Feb;97(2):97–104. doi: 10.1111/j.1699-0463.1989.tb00762.x. [DOI] [PubMed] [Google Scholar]
  45. Robbins R. A., Barnes P. J., Springall D. R., Warren J. B., Kwon O. J., Buttery L. D., Wilson A. J., Geller D. A., Polak J. M. Expression of inducible nitric oxide in human lung epithelial cells. Biochem Biophys Res Commun. 1994 Aug 30;203(1):209–218. doi: 10.1006/bbrc.1994.2169. [DOI] [PubMed] [Google Scholar]
  46. Rosenkranz-Weiss P., Sessa W. C., Milstien S., Kaufman S., Watson C. A., Pober J. S. Regulation of nitric oxide synthesis by proinflammatory cytokines in human umbilical vein endothelial cells. Elevations in tetrahydrobiopterin levels enhance endothelial nitric oxide synthase specific activity. J Clin Invest. 1994 May;93(5):2236–2243. doi: 10.1172/JCI117221. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. Sachdev H. P., Chadha V., Malhotra V., Verghese A., Puri R. K. Rectal histopathology in endemic Shigella and Salmonella diarrhea. J Pediatr Gastroenterol Nutr. 1993 Jan;16(1):33–38. doi: 10.1097/00005176-199301000-00007. [DOI] [PubMed] [Google Scholar]
  48. Saegusa M., Takano Y., Kishimoto H., Wakabayashi G., Nohga K., Okudaira M. Comparative analysis of p53 and c-myc expression and cell proliferation in human hepatocellular carcinomas--an enhanced immunohistochemical approach. J Cancer Res Clin Oncol. 1993;119(12):737–744. doi: 10.1007/BF01195346. [DOI] [PubMed] [Google Scholar]
  49. Sansonetti P. J., Ryter A., Clerc P., Maurelli A. T., Mounier J. Multiplication of Shigella flexneri within HeLa cells: lysis of the phagocytic vacuole and plasmid-mediated contact hemolysis. Infect Immun. 1986 Feb;51(2):461–469. doi: 10.1128/iai.51.2.461-469.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  50. Schmieg F. I., Simmons D. T. Characterization of the in vitro interaction between SV40 T antigen and p53: mapping the p53 binding site. Virology. 1988 May;164(1):132–140. doi: 10.1016/0042-6822(88)90628-9. [DOI] [PubMed] [Google Scholar]
  51. Searle J., Kerr J. F., Bishop C. J. Necrosis and apoptosis: distinct modes of cell death with fundamentally different significance. Pathol Annu. 1982;17(Pt 2):229–259. [PubMed] [Google Scholar]
  52. Shaw P., Bovey R., Tardy S., Sahli R., Sordat B., Costa J. Induction of apoptosis by wild-type p53 in a human colon tumor-derived cell line. Proc Natl Acad Sci U S A. 1992 May 15;89(10):4495–4499. doi: 10.1073/pnas.89.10.4495. [DOI] [PMC free article] [PubMed] [Google Scholar]
  53. Soini Y., Kamel D., Nuorva K., Lane D. P., Vähäkangas K., Päkkö P. Low p53 protein expression in salivary gland tumours compared with lung carcinomas. Virchows Arch A Pathol Anat Histopathol. 1992;421(5):415–420. doi: 10.1007/BF01606914. [DOI] [PubMed] [Google Scholar]
  54. Soini Y., Kamel D., Päkkö P., Lehto V. P., Oikarinen A., Vähäkangas K. V. Aberrant accumulation of p53 associates with Ki67 and mitotic count in benign skin lesions. Br J Dermatol. 1994 Oct;131(4):514–520. doi: 10.1111/j.1365-2133.1994.tb08552.x. [DOI] [PubMed] [Google Scholar]
  55. Soini Y., Vähäkangas K., Nuorva K., Kamel D., Lane D. P., Päkkö P. p53 immunohistochemistry in malignant fibrous histiocytomas and other mesenchymal tumours. J Pathol. 1992 Sep;168(1):29–33. doi: 10.1002/path.1711680106. [DOI] [PubMed] [Google Scholar]
  56. Speelman P., Kabir I., Islam M. Distribution and spread of colonic lesions in shigellosis: a colonoscopic study. J Infect Dis. 1984 Dec;150(6):899–903. doi: 10.1093/infdis/150.6.899. [DOI] [PubMed] [Google Scholar]
  57. Speelman P., McGlaughlin R., Kabir I., Butler T. Differential clinical features and stool findings in shigellosis and amoebic dysentery. Trans R Soc Trop Med Hyg. 1987;81(4):549–551. doi: 10.1016/0035-9203(87)90402-0. [DOI] [PubMed] [Google Scholar]
  58. Stieglitz H., Lipsky P. Association between reactive arthritis and antecedent infection with Shigella flexneri carrying a 2-Md plasmid and encoding an HLA-B27 mimetic epitope. Arthritis Rheum. 1993 Oct;36(10):1387–1391. doi: 10.1002/art.1780361010. [DOI] [PubMed] [Google Scholar]
  59. Struelens M. J., Patte D., Kabir I., Salam A., Nath S. K., Butler T. Shigella septicemia: prevalence, presentation, risk factors, and outcome. J Infect Dis. 1985 Oct;152(4):784–790. doi: 10.1093/infdis/152.4.784. [DOI] [PubMed] [Google Scholar]
  60. Szekely L., Pokrovskaja K., Jiang W. Q., Selivanova G., Löwbeer M., Ringertz N., Wiman K. G., Klein G. Resting B-cells, EBV-infected B-blasts and established lymphoblastoid cell lines differ in their Rb, p53 and EBNA-5 expression patterns. Oncogene. 1995 May 4;10(9):1869–1874. [PubMed] [Google Scholar]
  61. Veress B., Reinholt F. P., Lindquist K., Liljeqvist L. Different types of mucosal adaptation in the ileal reservoir after restorative proctocolectomy. A two-year follow-up study. APMIS. 1990 Sep;98(9):786–796. doi: 10.1111/j.1699-0463.1990.tb04999.x. [DOI] [PubMed] [Google Scholar]
  62. Wiman K. G. The retinoblastoma gene: role in cell cycle control and cell differentiation. FASEB J. 1993 Jul;7(10):841–845. doi: 10.1096/fasebj.7.10.8393817. [DOI] [PubMed] [Google Scholar]
  63. Wyllie A. H. Apoptosis and the regulation of cell numbers in normal and neoplastic tissues: an overview. Cancer Metastasis Rev. 1992 Sep;11(2):95–103. doi: 10.1007/BF00048057. [DOI] [PubMed] [Google Scholar]
  64. Xie Q. W., Whisnant R., Nathan C. Promoter of the mouse gene encoding calcium-independent nitric oxide synthase confers inducibility by interferon gamma and bacterial lipopolysaccharide. J Exp Med. 1993 Jun 1;177(6):1779–1784. doi: 10.1084/jem.177.6.1779. [DOI] [PMC free article] [PubMed] [Google Scholar]
  65. Yamaguchi A., Makimoto K., Goi T., Takeuchi K., Maehara M., Isobe Y., Nakagawara G. Overexpression of p53 protein and proliferative activity in colorectal adenoma. Oncology. 1994 May-Jun;51(3):224–227. doi: 10.1159/000227338. [DOI] [PubMed] [Google Scholar]
  66. Zychlinsky A., Fitting C., Cavaillon J. M., Sansonetti P. J. Interleukin 1 is released by murine macrophages during apoptosis induced by Shigella flexneri. J Clin Invest. 1994 Sep;94(3):1328–1332. doi: 10.1172/JCI117452. [DOI] [PMC free article] [PubMed] [Google Scholar]
  67. Zychlinsky A., Kenny B., Ménard R., Prévost M. C., Holland I. B., Sansonetti P. J. IpaB mediates macrophage apoptosis induced by Shigella flexneri. Mol Microbiol. 1994 Feb;11(4):619–627. doi: 10.1111/j.1365-2958.1994.tb00341.x. [DOI] [PubMed] [Google Scholar]
  68. Zychlinsky A., Prevost M. C., Sansonetti P. J. Shigella flexneri induces apoptosis in infected macrophages. Nature. 1992 Jul 9;358(6382):167–169. doi: 10.1038/358167a0. [DOI] [PubMed] [Google Scholar]
  69. van Bohemen C. G., Nabbe A. J., Landheer J. E., Grumet F. C., Mazurkiewicz E. S., Dinant H. J., Lionarons R. J., van Bodegom P. C., Zanen H. C. HLA-B27M1M2 and high immune responsiveness to Shigella flexneri in post-dysenteric arthritis. Immunol Lett. 1986 Aug;13(1-2):71–74. doi: 10.1016/0165-2478(86)90128-8. [DOI] [PubMed] [Google Scholar]

Articles from Infection and Immunity are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES