The immune system of the ferret (Mustela putorius furo) – A review

Hundakova A, Toman M, Knotek Z (2022): The immune system of the ferret (Mustela putorius furo) – A review. Vet Med-Czech 67, 408–417.

download PDF

The basic information dealing with the anatomy of the ferret’s immune system, cross-reactivity of the ferret leukocytes with polyclonal and monoclonal antibodies in vitro and immune response to the mitogens and various infections are presented. The leukocyte numbers in the peripheral blood in the ferrets are lower compared to other species and only one subclass of IgG has been identified in ferrets so far. Lymphocytes make up 12–67% of all the leukocytes in the peripheral blood of the healthy adult ferrets. Lymphocyte subpopulations are similar to other mammals and include T- and B-lymphocytes. T-lymphocytes differentiate into helper (Th) lymphocytes and cytotoxic (Tc) lymphocytes. Currently, ferret granulocytes (CD11), B-lymphocytes (CD79α), T-lymphocytes (CD3), Th-lymphocytes (CD3, CD4), Tc-lymphocytes (CD3, CD8), and CD30, CD45 subpopulations are detected with the use of a number of polyclonal as well as with monoclonal antibodies. In a lymphocyte transformation assay, the mitogen response of the peripheral blood mononuclear cells to concanavalin A (ConA), phytohaemagglutinin (PHA), and pokeweed mitogen (PWM) is the greatest at day 2, 2 and 3, respectively. Serious lymphopenia is observed in ferrets during a distemper infection. A significant decrease in the lymphocyte transformation activity is observed on day 5 and reaches a maximal decrease on days 8–11, with full recovery on days 23–30 after the inoculation of laboratory ferrets with the distemper virus. Ferrets have also been used in studies related to the function of the immune system in Helicobacter pylori infections, Crohn’s disease and bronchial asthma.

Aasted B. Mink infected with Aleutian disease virus have an elevated level of CD8-positive T-lymphocytes. Vet Immunol Immunopathol. 1989 Mar;20(4):375-85.
Albrecht RA, Liu WC, Sant AJ, Tompkins SM, Pekosz A, Meliopoulos V, Cherry S, Thomas PG, Schultz-Cherry S. Moving forward: Recent developments for the ferret biomedical research model. mBio. 2018 Jul 17;9(4):e01113-8.
Ammersbach M, Delay J, Caswell JL, Smith DA, Taylor WM, Bienzle D. Laboratory findings, histopathology, and immunophenotype of lymphoma in domestic ferrets. Vet Pathol. 2008 Sep;45(5):663-73.
Antinoff N, Hahn K. Ferret oncology: Diseases, diagnostics, and therapeutics. Vet Clin North Am Exot Anim Pract. 2004 Sep;7(3):579-625.
Belser JA, Katz JM, Tumpey TM. The ferret as a model organism to study influenza A virus infection. Dis Model Mech. 2011 Sep;4(5):575-9.
Blomme EA, Foy SH, Chappell KH, La Perle KM. Hypereosinophilic syndrome with Hodgkin’s-like lymphoma in a ferret. J Comp Pathol. 1999 Feb;120(2):211-7.
Cameron MJ, Kelvin AA, Leon AJ, Cameron CM, Ran L, Xu L, Chu YK, Danesh A, Fang Y, Li Q, Anderson A, Couch RC, Paquette SG, Fomukong NG, Kistner O, Lauchart M, Rowe T, Harrod KS, Jonsson CB, Kelvin DJ. Lack of innate interferon responses during SARS coronavirus infection in a vaccination and reinfection ferret model. PLoS One. 2012;7(9):e45842.
Campbell TW, Ellis CK. Avian and exotic animal hematology and cytology. In: Campbell TW, Ellis CK, editors. Hematology of small mammals. 3rd ed. Iowa, USA: Blackwell Publishing; 2007. p. 113-38.
Chan KF, Carolan LA, Druce J, Chappell K, Watterson D, Young P, Korenkov D, Subbarao K, Barr IG, Laurie KL, Reading PC. Pathogenesis, humoral immune responses, and transmission between cohoused animals in a ferret model of human respiratory syncytial virus infection. J Virol. 2018 Jan 30;92(4):e01322-17.
Cheng X, Zengel JR, Suguitan AL Jr, Xu Q, Wang W, Lin J, Jin H. Evaluation of the humoral and cellular immune responses elicited by the live attenuated and inactivated influenza vaccines and their roles in heterologous protection in ferrets. J Infect Dis. 2013 Aug 15;208(4):594-602.
Chu YK, Ali GD, Jia F, Li Q, Kelvin D, Couch RC, Harrod KS, Hutt JA, Cameron C, Weiss SR, Jonsson CB. The SARS-CoV ferret model in an infection-challenge study. Virology. 2008 Apr 25;374(1):151-63.
Clyne M, Ocroinin T, Suerbaum S, Josenhans C, Drumm B. Adherence of isogenic flagellum-negative mutants of Helicobacter pylori and Helicobacter mustelae to human and ferret gastric epithelial cells. Infect Immun. 2000 Jul;68(7):4335-9.
Coleman LA. Immunophenotypic characterization of lymphoid tissue and lymphoproliferative disease in ferrets (Mustela putorious furo) [Master’s thesis]. Cambridge, Massachusetts, USA: Massachusetts Institute of Technology; 1997.
Crevel R. Lymphocyte proliferation. In: Vohr HW, editor. Encyclopedic reference of immunotoxicology. Berlin, Heidelberg: Springer; 2005. p. 401-5.
Cross ML, Labes RE, Mackintosh CG. Oral infection of ferrets with virulent Mycobacterium bovis or Mycobacterium avium: Susceptibility, pathogenesis and immune response. J Comp Pathol. 2000 Jul;123(1):15-21.
DiPiazza A, Richards K, Batarse F, Lockard L, Zeng H, Garcia-Sastre A, Albrecht RA, Sant AJ. Flow cytometric and cytokine ELISpot approaches to characterize the cell-mediated immune response in ferrets following influenza virus infection. J Virol. 2016 Aug 12;90(17):7991-8004.
Duncan JR. The lymph nodes. In: Cowell RL, Tyler RD, editors. Diagnostic cytology of the dog and cat. Santa Barbara, USA: American Veterinary Publications; 1989. p. 94.
Ellis C. Ferrets. In: Birchard SJ, Sherding RG, editors. Saunders’ manual of small animal practice. 3rd ed. St. Louis, MO, USA: Saunders Elsevier; 2006. p. 1816-57.
Evans EH, An QN. Anatomy of the ferret. In: Fox JG, editor. Biology and diseases of the ferret. 2nd ed. Philadelphia, USA: Williams & Wilkins; 1999. p. 19-69.
Fox JG, Correa P, Taylor NS, Lee A, Otto G, Murphy JC, Rose R. Helicobacter mustelae-associated gastritis in ferrets. An animal model of Helicobacter pylori gastritis in humans. Gastroenterology. 1990 Aug;99(2):352-61.
Fox JG. Taxonomy, history, and use. In: Fox JG, editor. Biology and diseases of the ferret. 2nd ed. Philadelphia, USA: Williams & Wilkins; 1999a. p. 3-8.
Fox JG. Normal clinical and biologic parameters. In: Fox JG, editor. Biology and diseases of the ferret. 2nd ed. Philadelphia, USA: Williams & Wilkins; 1999b. p. 183-210.
Fox JG. Normal clinical and biological parameters. In: Fox JG, Marini RP, editors. Biology and diseases of ferret. 3rd ed. Iowa, USA: Wiley Blackwell; 2014. p. 157-85.
Fujishiro T, Honjo M, Kawasaki H, Asaoka R, Yamagishi R, Aihara M. Structural changes and astrocyte response of the lateral geniculate nucleus in a ferret model of ocular hypertension. Int J Mol Sci. 2020 Feb 17;21(4):1339.
Garcia DAA, Silva LCS, Lange RR, Froes TR. Anatomia ultrassonografica dos linfonodos abdominais de furoes europeus higidos [Ultrasonographic anatomy of abdominal lymph nodes in the normal ferret]. Pesq Vet Bras. 2011;31(12):1129-32. Spanish.
Gollakner R, Capua I. Is COVID-19 the first pandemic that evolves into a panzootic? Vet Ital. 2020 Apr 24;56(1):11-2.
Gupta A, Gumber S, Schnellbacher R, Bauer RW, Gaunt SD. Malignant B-cell lymphoma with Mott cell differentiation in a ferret (Mustela putorius furo). J Vet Diagn Invest. 2010 May;22(3):469-73.
Hammer AS, Williams B, Dietz HH, Hamilton-Dutoit SJ. High-throughput immunophenotyping of 43 ferret lymphomas using tissue microarray technology. Vet Pathol. 2007 Mar;44(2):196-203.
Ingrao JC, Eshar D, Vince A, Lee-Chow B, Nykamp S, DeLay J, Smith D. Focal thoracolumbar spinal cord lymphosarcoma in a ferret (Mustela putorius furo). Can Vet J. 2014 Jul;55(7):667-71.
Jin H, Manetz S, Leininger J, Luke C, Subbarao K, Murphy B, Kemble G, Coelingh KL. Toxicological evaluation of live attenuated, cold-adapted H5N1 vaccines in ferrets. Vaccine. 2007 Dec 17;25(52):8664-72.
Kauffman CA, Schiff GM, Phair JP. Influenza in ferrets and guinea pigs: Effect on cell-mediated immunity. Infect Immun. 1978 Feb;19(2):547-52.
Kauffman CA, Bergman AG, O’Connor RP. Distemper virus infection in ferrets: An animal model of measles-induced immunosuppression. Clin Exp Immunol. 1982 Mar;47(3):617-25.
Kawasaki H, Crowley JC, Livesey FJ, Katz LC. Molecular organization of the ferret visual thalamus. J Neurosci. 2004 Nov 3;24(44):9962-70.
Kim YI, Kim SG, Kim SM, Kim EH, Park SJ, Yu KM, Chang JH, Kim EJ, Lee S, Casel MAB, Um J, Song MS, Jeong HW, Lai VD, Kim Y, Chin BS, Park JS, Chung KH, Foo SS, Poo H, Mo IP, Lee OJ, Webby RJ, Jung JU, Choi YK. Infection and rapid transmission of SARS-CoV-2 in ferrets. Cell Host Microbe. 2020 May 13;27(5):704-9.
Kirchenbaum GA, Ross TM. Generation of monoclonal antibodies against immunoglobulin proteins of the domestic ferret (Mustela putorius furo). J Immunol Res. 2017;2017:5874572.
Knotkova Z. Laboratorni metody – Hematologie [Laboratory methods – Haematology]. In: Knotek Z, editor. Nemoci zajmovych zvirat – Drobni savci [Diseases of companion animals – Small mammals]. Praha: Profi Press s.r.o.; 2017. p. 280-5.Czech.
Ko J, Marini RP. Anesthesia and analgesia in ferrets. In: Fish R, Danneman PJ, Brown M, Karas A, editors. Anesthesia and analgesia in laboratory animals. London: Academic Press; 2011. p. 449-55.
Layton DS, Xiao X, Bentley JD, Lu L, Stewart CR, Bean AG, Adams TE. Development of an anti-ferret CD4 monoclonal antibody for the characterisation of ferret T lymphocytes. J Immunol Methods. 2017 May;444:29-35.
Lennox AM. The anemic ferret: Where to go when the answer isn’t obvious. Proceedings of NAVC Conference 2012: Small Animal & Exotics Proceedings; 2012 Jan 14-18;Orlando, FL, USA. p. 1468.
Lewington JH. Classification, history and current status of ferrets. In: Lewington JH, editor. Ferret husbandry, medicine and surgery. 2nd ed. Edinburgh: Saunders Elsevier; 2007. p. 3-14.
Liang C, Rounds NK, Dong E, Stevens SY, Shite J, Qin F. Alterations by norepinephrine of cardiac sympathetic nerve terminal function and myocardial beta-adrenergic receptor sensitivity in the ferret: Normalization by antioxidant vitamins. Circulation. 2000 Jul 4;102(1):96-103.
Lu K, Liu W, Zan P, David SV, Fritz JB, Shamma SA. Implicit memory for complex sounds in higher auditory cortex of the ferret. J Neurosci. 2018 Nov 14;38(46):9955-66.
Maher JA, DeStefano J. The ferret: An animal model to study influenza virus. Lab Anim (NY). 2004 Oct;33(9):50-3.
Martel CJ, Aasted B. Characterization of antibodies against ferret immunoglobulins, cytokines and CD markers. Vet Immunol Immunopathol. 2009 Dec 15;132(2-4):109-15.
Martina BE, Haagmans BL, Kuiken T, Fouchier RA, Rimmelzwaan GF, Van Amerongen G, Peiris JS, Lim W, Osterhaus AD. Virology: SARS virus infection of cats and ferrets. Nature. 2003 Oct 30;425(6961):915.
Matsuoka Y, Lamirande EW, Subbarao K. The ferret model for influenza. Curr Protoc Microbiol. 2009 May;Chapter 15:Unit 15G.2.
Mayer J, Erdman SE, Fox JG. Diseases of the hematopoietic system. In: Fox JG, Marini RP, editors. Biology and diseases of ferret. 3rd ed. Iowa, USA: Wiley Blackwell; 2014. p. 311-34.
Mayer J, Marini RP, Fox JG. Biology in diseases of ferrets. In: Fox JG, editor. Laboratory animal medicine. 3rd ed. London: Academic Press; 2015. p. 577-621.
McLaren C, Butchko GM. Regional T- and B-cell responses in influenza-infected ferrets. Infect Immun. 1978 Oct;22(1):189-94.
Morgan JP, Travers KE. Use of ferret in cardiovascular research. In: Fox JG, editor. Biology and diseases of the ferret. 2nd ed. Philadelphia: Williams & Wilkins; 1999. p. 499-510.
Music N, Reber AJ, Kim JH, York IA. Peripheral leukocyte migration in ferrets in response to infection with seasonal influenza virus. PLoS One. 2016 Jun 17;11(6):e0157903.
Oh DY, Hurt AC. Using the ferret as an animal model for investigating influenza antiviral effectiveness. Front Microbiol. 2016 Feb 4;7:1-12.
Onuma M, Kondo H, Ono S, Shibuya H, Sato T. Cytomorphological and immunohistochemical features of lymphoma in ferrets. J Vet Med Sci. 2008 Sep;70(9):893-8.
Osborne MJ, Hudson M, Piasecki C, Dhillon AP, Lewis AA, Pounder RE, Wakefield AJ. Crohn’s disease and anastomotic recurrence: Microvascular ischaemia and anasto-motic healing in an animal model. Br J Surg. 1993 Feb;80(2):226-9.
Otte A, Marriott AC, Dreier C, Dove B, Mooren K, Klingen TR, Sauter M, Thompson KA, Bennett A, Klingel K, van Riel D, McHardy AC, Carroll MW, Gabriel G. Evolution of 2009 H1N1 influenza viruses during the pandemic correlates with increased viral pathogenicity and transmissibility in the ferret model. Sci Rep. 2016 Jun 24;6:28583.
Parker L, Gilliland SM, Minor P, Schepelmann S. Assessment of the ferret as an in vivo model for mumps virus infection. J Gen Virol. 2013 Jun;94(Pt 6):1200-5.
Parry NM. Overview of ferret lymphoma. Am Vet. 2018;3(2):12-3.
Patterson MM, Fox JG. The laboratory ferret. In: Prescott JS, editor. The clinical chemistry of laboratory animals. 3rd ed. Boca Raton, FL: Taylor & Francis Group; 2017. p. 1950-3.
Paul-Murphy J, O’Brien RT, Spaeth A, Sullivan L, Dubielzig RR. Ultrasonography and fine needle aspirate cytology of the mesenteric lymph node in normal domestic ferrets (Mustela putorius furo). Vet Radiol Ultrasound. 1999 May-Jun;40(3):308-10.
Pearson RC, Gorham JR. Viral disease models. In: Fox JG, editor. Biology and diseases of the ferret. 2nd ed. Philadelphia, USA: Williams & Wilkins; 1999. p. 487-97.
Perpinan D, Ramis A, Tomas A, Carpintero E, Bargalla F. Outbreak of canine distemper in domestic ferrets (Mustela putorius furo). Vet Rec. 2008 Aug 23;163(8):246-50.
Pillet S, Kobasa D, Meunier I, Gray M, Laddy D, Weiner DB, von Messling V, Kobinger GP. Cellular immune response in the presence of protective antibody levels correlates with protection against 1918 influenza in ferrets. Vaccine. 2011 Sep 9;29(39):6793-801.
Potter CW, Rees RC, Shore SL, Jennings R, McLaren C. Immunity to influenza in ferrets. IX. Delayed hypersensitivity following infection or immunization with A2/Hong Kong virus. Microbios. 1974 Jun-Jul;10A Suppl(41):7-21.
Powers LV, Brown SA. Basic anatomy, physiology and husbandry. In: Quesenberry K, Carpenter JW, editors. Ferrets, rabbits and rodents: Clinical medicine and surgery. 3rd ed. St. Louis, USA: Elsevier Health Sciences; 2012. p. 1-12.
Pyle NJ. Use of ferrets in laboratory work and research investigations. Am J Public Health Nations Health. 1940 Jul;30(7):787-96.
Quesenberry KE, Orcutt C. Basic approach to veterinary medicine. In: Quesenberry K, Carpenter JW, editors. Ferrets, rabbits and rodents: Clinical medicine and surgery. 3rd ed. St. Louis, USA: Elsevier Health Sciences; 2012. p. 13-26.
Rutigliano JA, Doherty PC, Franks J, Morris MY, Reynolds C, Thomas PG. Screening monoclonal antibodies for cross-reactivity in the ferret model of influenza infection. J Immunol Methods. 2008 Jul 20;336(1):71-7.
Schumacher WA, Steinbacher TE, Megill JR, Durham SK. A ferret model of electrical-induction of arterial thrombosis that is sensitive to aspirin. J Pharmacol Toxicol Methods. 1996 Feb;35(1):3-10.
Schwerin SC, Chatterjee M, Imam-Fulani AO, Radomski KL, Hutchinson EB, Pierpaoli CM, Juliano SL. Progression of histopathological and behavioral abnormalities following mild traumatic brain injury in the male ferret. J Neurosci Res. 2018 Apr;96(4):556-72.
Sherrill A, Gorham J. Bone marrow hypoplasia associated with estrus in ferrets. Lab Anim Sci. 1985 Jun;35(3):280-6.
Shi J, Wen Z, Zhong G, Yang H, Wang C, Huang B, Liu R, He X, Shuai L, Sun Z, Zhao Y, Liu P, Liang L, Cui P, Wang J, Zhang X, Guan Y, Tan W, Wu G, Chen H, Bu Z. Susceptibility of ferrets, cats, dogs, and other domesticated animals to SARS-coronavirus 2. Science. 2020 May 29;368(6494):1016-20.
Shoji Y, Bi H, Musiychuk K, Rhee A, Horsey A, Roy G, Green B, Shamloul M, Farrance CE, Taggart B, Mytle N, Ugulava N, Rabindran S, Mett V, Chichester JA, Yusibov V. Plant-derived hemagglutinin protects ferrets against challenge infection with the A/Indonesia/05/05 strain of avian influenza. Vaccine. 2009 Feb 11;27(7):1087-92.
Siperstein LJ. Ferret hematology and related disorders. Vet Clin North Am Exot Anim Pract. 2008 Sep;11(3):535-50.
Smith SA, Zimmerman K, Moore DM. Hematology of the domestic ferret (Mustela putorius furo). Vet Clin North Am Exot Anim Pract. 2015 Jan;18(1):1-8.
Stittelaar KJ, de Waal L, van Amerongen G, Veldhuis Kroeze EJ, Fraaij PL, van Baalen CA, van Kampen JJ, van der Vries E, Osterhaus AD, de Swart RL. Ferrets as a novel animal model for studying human respiratory syncytial virus infections in immunocompetent and immunocompromised hosts. Viruses. 2016 Jun 14;8(6):168.
Suran JN, Latney LV, Wyre NR. Radiographic and ultrasonographic findings of the spleen and abdominal lymph nodes in healthy domestic ferrets. J Small Anim Pract. 2017 Aug;58(8):444-53.
Swennes AG, Fox JG. Bacterial and mycoplasmal diseases. In: Fox JG, Marini RP, editors. Biology and diseases of ferret. 3rd ed. Iowa, USA: Wiley Blackwell; 2014. p. 519-52.
Szelenyi I. Animal models of bronchial asthma. Inflamm Res. 2000 Dec;49(12):639-54.
Tabel H, Ingram DG. Immunoglobulins of mink. Evidence for five immunoglobulin classes of 7S type. Immunology. 1972 J0un;22(6):933-42.
Taylor TG, Carpenter JL. Thymoma in two ferrets. Lab Anim Sci. 1995 Aug;45(4):363-5.
Trebichavsky I. Imunitni system a jeho funkce [Immune system and its functions]. In: Toman M, Barta O, Dostal J, Faldyna M, Hosan V, Hruban V, Jeklova E, Knotek Z et al., editors. Veterinarni imunologie [Veterinary immunology]. Praha: Grada Publishing; 2000. p. 17-100. Czech.
Vidana B, Majo N, Perez M, Montoya M, Martorell J, Martinez J. Immune system cells in healthy ferrets: An immunohistochemical study. Vet Pathol. 2014 Jul;51(4):775-86.
von Messling V, Springfeld C, Devaux P, Cattaneo R. A ferret model of canine distemper virus virulence and immunosuppression. J Virol. 2003 Dec;77(23):12579-91.
Warren BF, Watkins PE. Animal models of inflammatory bowel disease. J Pathol. 1994 Apr;172(4):313-6.
Williams BH, Wire NR. Neoplasia in ferrets. In: Quesenberry K, Man SC, Orcutt C, Carpenter JW, editors. Ferrets, rabbits and rodents: Clinical medicine and surgery. Philadelphia: Elsevier; 2020. p. 92-107.
Williams BH. Pathology of domestic ferret, instruction block. The joint pathology center [Internet]. 2010 [cited 2021 Jan 28]. Available from:
Wong J, Layton D, Wheatley AK, Kent SJ. Improving immunological insights into the ferret model of human viral infectious disease. Influenza Other Respir Viruses. 2019 Nov;13(6):535-46.
Wong J, Tai CM, Hurt AC, Tan HX, Kent SJ, Wheatley AK. Sequencing B cell receptors from ferrets (Mustela putorius furo). PLoS One. 2020 May 29;15(5):e0233794.
Wu A, Zheng H, Kraenzle J, Biller A, Vanover CD, Proctor M, Sherwood L, Steffen M, Ng C, Mollura DJ, Jonsson CB. Ferret thoracic anatomy by 2-deoxy-2-(18F)fluoro-d-glucose (18F-FDG) positron emission tomography/computed tomography (18F-FDG PET/CT) imaging. ILAR J. 2012;53(1):E9-21.
Wyllie SE, Kelman M, Ward MP. Epidemiology and clinical presentation of canine distemper disease in dogs and ferrets in Australia, 2006–2014. Aust Vet J. 2016 Jul;94(7):215-22.
download PDF

© 2022 Czech Academy of Agricultural Sciences | Prohlášení o přístupnosti