Saeed AL-RAMADAN, Kazem AL-MOHAMMED SALEM, Ibrahim ALSHUBAITH, Ahmed ALLUWAIMI

CD markers of camel (Camelus dromedarius) intestine naturally infected with Mycobacterium avium subsp. paratuberculosis: Distinct expression of Madcam-1 and CX3CR1

Mycobacteriumavium subsp. paratuberculosis (MAP) infection in camel requires extensive research, particularly the immune responses in the intestine. This study aimed to investigate the nature of the cellular populations that are driven by the immunopathological responses in the camel intestine infected with MAP at different ages. Immunohistochemical staining was carried out on tissues obtained from naturally infected young (5–10 years old) and older (12–15 years old) camels. The staining of the tissues, ileum, mesenteric lymph node, jejunum, and supramammary lymph nodes, with anti-CD3+, CD4+, CD8+, CD25+, CD11c+, CD14+, WC1+, CX3CR1, and Madcam-1 monoclonal antibodies revealed high expression of the molecules CD8+, CD25+, CD11c+, CD14+, WC1+, CX3CR1, and Madcam-1 in the ileum and mesenteric lymph node of the infected older camels. The results indicated the recruitment of CD8+ lymphocytes, CD14+ macrophages, and CD11c+ dendritic cells to the ileal lamina propria. High expression of CX3CR1 could indicate a vital role for this special macrophage phenotype in the ileal lamina propria in maintaining intestinal homeostasis. Madcam-1 expression could have an essential role in defining the nature of the recruited cells to the site of the infection. Expression of CX3CR1 and Madcam-1 is a novel finding that merits further attention and pursuit to reveal their significance in the immune responses to MAP in the camel’s intestine.

PDF

___

1. Stabel JR. Johne’s disease: A hidden threat. Journal of Dairy Science 1997; 81 (1): 283-288. doi: 10.3168/jds.S0022- 0302(98)75577-8
2. Al Hajri SM, Alluwaimi AM. ELISA and PCR for evaluation of subclinical paratuberculosis in the Saudi dairy herds. Veterinary Microbiology 2007; 121 (3-4): 384-385. doi: 10.1016/j.vetmic.2007.01.025.
3. Al-Dubaib MA, Mahmoud OM. Paratuberculosis of goats at Qassim region of Central Saudi Arabia. Bulgarian Journal of Veterinary Medicine 2008; 11 (1): 65-69.
4. Alhebabi, A.M. and Alluwaimi, A.M. Paratuberculosis in Camel (Camelus dromedarius): The Diagnostic Efficiency of ELISA and PCR. Open Veterinary Science Journal 2010; 4: 41- 44. doi:10.2174/1874318801004010041.
5. Alluwaimi A, Hatem M, Almousa J. The efficacy of gel immunodiffusion and fecal smear tests for diagnosis of ovine paratuberculosis in sheep in Saudi Arabia. Egyptian Journal of Immunology 2000; 7 (2): 29-32.
6. Beard PM, Daniels MJ, Henderson D, Pirie A, Rudge K et al. Paratuberculosis infection of nonruminant wildlife in Scotland. Journal of Clinical Microbiology 2001; 39 (4): 1517- 1521. doi: 10.1128/JCM.39.4.1517-1521.2001.
7. Sweeney R, Jones D, Habecker P, Scott P. Interferon-gamma and interleukin 4 gene expression in cows infected with Mycobacterium paratuberculosis. American journal of veterinary research 1998; 59 (7): 842-847.
8. Alluwaimi AM, Badi FA. Mycobacterium avium subspecies paratuberculosis infection in naturally infected cattle is associated with an upregulation of lipid metabolism gene expression. International journal of Advanced Life Sciences 2015; 8 (4): 377-397.
9. Thirunavukkarasu S, Plain KM, de Silva K, Begg D, Whittington RJ et al. Expression of genes associated with cholesterol and lipid metabolism identified as a novel pathway in the early pathogenesis of Mycobacterium avium subspecies paratuberculosis-infection in cattle. Veterinary immunology and immunopathology 2014; 160 (3-4): 147-157. doi. org/10.1016/j.vetimm.2014.04.002.
10. Arsenault RJ, Maattanen P, Daigle J, Potter A, Griebel P et al. From mouth to macrophage: mechanisms of innate immune subversion by Mycobacterium avium subsp. paratuberculosis. Veterrinary Research 2014; 45 (1): 1-15. doi: 10.1186/1297- 9716-45-54.
11. Sweeney RW, Uzonna J, Whitlock RH, Habecker PL, Chilton P et al. Tissue predilection sites and effect of dose on Mycobacterium avium subs. paratuberculosis organism recovery in a short-term bovine experimental oral infection model. Research in Veterinary Science 2006; 80 (3): 253-259. doi.org/10.1016/j.rvsc.2005.07.007.
12. Sigurethardottir OG, Valheim M, Press CM. Establishment of Mycobacterium avium subsp. paratuberculosis infection in the intestine of ruminants. Advanced Drug Delivery Reviews 2004; 56 (6): 819-834. doi: 10.1016/j.addr.2003.10.032.
13. Koets AP, Eda S, Sreevatsan S. The within host dynamics of Mycobacterium avium ssp. paratuberculosis infection in cattle: where time and place matter. Veterinary research 2015; 46 (1): 61. doi: 10.1186/s13567-015-0185-0.
14. Charavaryamath C, Gonzalez-Cano P, Fries P, Gomis S, Doig K et al. Host responses to persistent Mycobacterium avium subspecies paratuberculosis infection in surgically isolated bovine ileal segments. Clinical and Vaccine Immunology 2013; 20 (2): 156-165. doi: 10.1128/CVI.00496-12
15. Lei L, Plattner BL, Hostetter JM. Live Mycobacterium avium subsp. paratuberculosis and a killed-bacterium vaccine induce distinct subcutaneous granulomas, with unique cellular and cytokine profiles. Clinical and Vaccine Immunology 2008; 15 (5): 783-793. doi: 10.1128/CVI.00480-07.
16. Navarro JA, Ramis G, Seva J, Pallares FJ, Sanchez J. Changes in lymphocyte subsets in the intestine and mesenteric lymph nodes in caprine paratuberculosis. Journal of Comparative Pathology 1998; 118 (2): 109-121. doi: 10.1016/s0021- 9975(98)80003-0.
17. Valheim M, Sigurdardottir OG, Storset AK, Aune LG, Press C.M. Characterization of macrophages and occurrence of T cells in intestinal lesions of subclinical paratuberculosis in goats. Journal of Comparative Pathology 2004; 131 (2-3): 221- 232. doi: 10.1016/j.jcpa.2004.04.004.
18. Zola, H., Swart, B., Nicholson, I., & Voss, E. Leukocyte and stromal cell molecules: the CD markers. John Wiley & Sons 2007. ISBN 13: 9780471701323
19. Ernst JD. Macrophage receptors for Mycobacterium tuberculosis. Infection and Immunity 1998; 66 (4): 1277-1281. doi.org/10.1128/IAI.66.4.1277-1281.1998.
20. Chen C, Herzig CT, Telfer JC, Baldwin CL. Antigenic basis of diversity in the gammadelta T cell co-receptor WC1 family. Molecular Immunology 2009; 46 (3): 2565-2575. doi: 10.1016/j. molimm.2009.05.010.
21. Rogers AN, Vanburen DG, Hedblom EE, Tilahun ME, Telfer JC et al . Gammadelta T cell function varies with the expressed WC1 coreceptor. The Journal of Immunology 2005; 174 (6): 3386-3393. doi: 10.4049/jimmunol.174.6.3386.
22. Clahsen T, Pabst O, Tenbrock K, Schippers A, Wagner N. Localization of dendritic cells in the gut epithelium requires MAdCAM-1. Clinical Immunology 2015; 156 (1): 74-84. doi: 10.1016/j.clim.2014.11.005.
23. Nagamatsu H, Tsuzuki Y, Matsuzaki K, Miyazaki J, Okada Y et al. Regulation of T-lymphocyte trafficking by ICAM-1, MAdCAM-1, and CCR7 in microcirculation of appendicular and intestinal lymphoid tissues. Microcirculation 2004; 11 (6): 493-502. doi: 10.1080/10739680490476079.
24. Al-Ashqar RA, Salem KMA-M, Al Herz AKM, Al-Haroon AI, Alluwaimi AM. The CD markers of camel (Camelus dromedarius) milk cells during mastitis: The LPAM-1 expression is an indication of possible mucosal nature of the cellular trafficking. Research in Veterinary Science 2015; 99: 77-81. doi.org/10.1016/j.rvsc. 2015.01.011
25. Al-Mohammed Salem K, Al Ramadan S, Alluwaimi A. Adhesion Molecules and the Cellular Population of the Normal Camel (Camelus dromedaries) Mammary Glands. The Open Veterinary Science Journal 2012; 6 (1): 15-22. doi.org/10.2174/ 1874318801206010015.
26. Al-Mohammed Salem K, Badi FA, Al-Haroon AI, Alluwaimi AM. The Cellular Population of Normal Camel (Camelus dromedaries) Milk. Open Journal of Veterinary Medicine 2012; 6: 15-22. doi:10.4236/ojvm.2012.24042
27. Regoli M, Bertelli E, Gulisano M, Nicoletti C. The Multifaceted Personality of Intestinal CX3CR1+ Macrophages. Trend in Immunology 2017; 38 (12): 879-886. doi: 10.1016/j. it.2017.07.009
28. Alharbi KB, Al-Swailem A, Al-Dubaib MA, Al-Yamani E, Al-Naeem A et al.Pathology and molecular diagnosis of paratuberculosis of camels. Tropical animal health and production 2012; 44 (1): 173-177. doi: 10.1007/s11250-011- 9905-2.
29. Almujalli A, Al Ghamdi G. Clinicopathological findings of paratuberculosis in camels: possible steps for control strategy. Research Journal of Biological Sciences 2012; 7 (3): 128-131. doi: 10.3923/rjbsci.2012.128.131
30. El-Deeb W, Fouda T, El-Bahr S. Clinico-biochemical investigation of paratuberculosis of dromedary camels in Saudi Arabia: proinflammatory cytokines, acute phase proteins and oxidative stress biomarkers. Pakistan Veterinary Journal 2014; 34 (4): 484-488.
31. Gameel A, Ali A, Razig S, Brown J. A clinico-pathological study on spontaneous paratuberculosis in camels (Camelus dromedarius) in Saudi Arabia. Pakistan Veterinary Journal 1994; 14 (3): 160-162.
32. Hereba A, Hamouda M, Al-hizab F. Johne’s disease in dromedary camel: Gross findings, histpathology and PCR. Journal of Camel Practice and Research 2014; (1): 21, 83-88. doi : 10.5958/2277-8934.2014.00016.2.
33. Tharwat M, Al-Sobayil F, Ali A, Buczinski S. Transabdominal ultrasonographic appearance of the gastrointestinal viscera of healthy camels (Camelus dromedaries). Research in veterinary science 2012; 93 (2): 1015-1020. doi: 10.1016/j. rvsc.2011.12.003.
34. Bancroft JD, Cook HC. Manual of histological techniques and their diagnostic application. Churchill Livingstone 1994.
35. Shan, Ling, et al. “Combination of conventional immunohisto chemistry and qRT-PCR to detect ALK rearrangement.” Diagnostic pathology 9.1 (2014): 3. doi:10.1186/1746-1596-9-3.
36. Wu CW, Livesey M, Schmoller SK, Manning EJ, Steinberg H et al. Invasion and persistence of Mycobacterium avium subsp. paratuberculosis during early stages of Johne’s disease in calves. Infection and Immunity 2007; 75 (5): 2110-2119. doi: 10.1128/ IAI.01739-06.
37. Schenk M, Mueller C. Adaptations of intestinal macrophages to an antigen-rich environment. Seminars in Immunology 2007; 19 (2): 84-93. doi: 10.1016/j.smim.2006.09.002.
38. Sun M, He C, Cong Y, Liu Z. Regulatory immune cells in regulation of intestinal inflammatory response to microbiota. Mucosal Immunology 2015; 8 (5): 969-978. doi: 10.1038/ mi.2015.49.
39. Alluwaimi AM. Paratuberculosis Infection in Camel (Camelus dromedarius): Current and Prospective Overview. Open Journal of Veterinary Medicine 2015; 5 (7): 153.
40. Plattner BL, Huffman E, Jones DE, Hostetter JM. T lymphocyte responses during early enteric Mycobacterium avium subspecies paratuberculosis infection in cattle. Veterinary Immunology and Immunopathology 2014; 157 (1-2): 12-19. doi.org/10.1016/j.vetimm.2013.11.001
41. Toms C, Powrie F. Control of intestinal inflammation by regulatory T cells. Microbes and Infection 2001; 3 (11): 929- 935. doi: 10.1016/s1286-4579(01)01454-x.
42. Coussens PM, Sipkovsky S, Murphy B, Roussey J, Colvin CJ. Regulatory T cells in cattle and their potential role in bovine paratuberculosis. Comparative Immunology, Microbiology and Infectious Disease 2012; 35 (3): 233-239. doi: 10.1016/j. cimid.2012.01.004.
43. Wang F, Herzig C, Ozer D, Baldwin CL, Telfer JC. Tyrosine phosphorylation of scavenger receptor cysteine‐rich WC1 is required for the WC1‐mediated potentiation of TCR‐induced T‐cell proliferation. European Journal of Immunology. 2009; 39 (1): 254-266. doi: 10.1002/eji.200838472.
44. Albarrak SM, Waters WR, Stabel JR, Hostetter JM. Evaluating the cytokine profile of the WC1(+) gammadelta T cell subset in the ileum of cattle with the subclinical and clinical forms of MAP infection. Veterinary Immunology and Immunopathology 2018; 201: 26-31. doi.org/10.1016/j.vetimm. 2018.05.003.
45. Weiss D, Souza C. Review paper: modulation of mononuclear phagocyte function by Mycobacterium avium subsp. paratuberculosis. Veterinary Pathology Online 2008; 45 (6): 829-841. doi: 10.1354/vp.45-6-829
46. Gren, S. T., & Grip, O. Role of monocytes and intestinal macrophages in Crohn’s disease and ulcerative colitis. Inflammatory bowel diseases2016; 22 (8): 1992-1998. doi: 10.1097/MIB.0000000000000824.
47. Alluwaimi, A. M. The etiology of Mycobacterium avium subspecies paratuberculosis in Crohn’s disease. Saudi medical journal 2007; 28 (10): 1479.