Minipigs in Translational Immunosafety Sciences

The porcine immune system has been studied especially with regard to infectious diseases of the domestic pig, highlighting the economic importance of the pig in agriculture. Recently, in particular, minipigs have received attention as alternative species to dogs or nonhuman primates in drug safety evaluations. The increasing number of new drug targets investigated to modulate immunological pathways has triggered renewed interest to further explore the porcine immune system. Comparative immunological studies of minipigs with other species broaden the translational models investigated in drug safety evaluations. The porcine immune system overall seems functionally similar to other mammalian species, but there are some anatomical, immunophenotypical, and functional differences. Here, we briefly review current knowledge of the innate and adaptive immune system in pigs and minipigs. In conclusion, more systematic and cross-species comparisons are needed to assess the significance of immunological findings in minipigs in the context of translational safety sciences.

[1]  V. Bordignon,et al.  Efficacy of the porcine species in biomedical research , 2015, Front. Genet..

[2]  Wei-hua Zhao,et al.  The IL‐33/ST2 axis is specifically required for development of adipose tissue‐resident regulatory T cells , 2015, Cellular and Molecular Immunology.

[3]  Nicole von Burg,et al.  Maintenance of Immune Homeostasis through ILC/T Cell Interactions , 2015, Front. Immunol..

[4]  L. van de Laar,et al.  A Hitchhiker’s Guide to Myeloid Cell Subsets: Practical Implementation of a Novel Mononuclear Phagocyte Classification System , 2015, Front. Immunol..

[5]  W. Gerner,et al.  Phenotypic and functional differentiation of porcine αβ T cells: current knowledge and available tools. , 2015, Molecular immunology.

[6]  O. Sundnes,et al.  Epidermal Expression and Regulation of Interleukin-33 during Homeostasis and Inflammation: Strong Species Differences. , 2015, The Journal of investigative dermatology.

[7]  F. Meurens,et al.  The immunology of the porcine skin and its value as a model for human skin. , 2015, Molecular immunology.

[8]  M. Sinkora,et al.  The distribution of lymphoid cells in the small intestine of germ-free and conventional piglets. , 2015, Developmental and comparative immunology.

[9]  F. Meurens,et al.  Special issue on non-rodent animal models for immunology research: what can we learn from large animals? , 2015, Molecular Immunology.

[10]  L. Jouneau,et al.  Defining Mononuclear Phagocyte Subset Homology Across Several Distant Warm-Blooded Vertebrates Through Comparative Transcriptomics , 2015, Front. Immunol..

[11]  R. Locksley,et al.  Interleukin-33 in Tissue Homeostasis, Injury, and Inflammation. , 2015, Immunity.

[12]  N. Bertho,et al.  Investigating Evolutionary Conservation of Dendritic Cell Subset Identity and Functions , 2015, Front. Immunol..

[13]  S. Donovan,et al.  Human Microbiota-Associated Swine: Current Progress and Future Opportunities , 2015, ILAR journal.

[14]  R. Dürrwald,et al.  Magnitude and kinetics of multifunctional CD4+ and CD8β+ T cells in pigs infected with swine influenza A virus , 2015, Veterinary Research.

[15]  W. Gerner,et al.  Natural and inducible Tregs in swine: Helios expression and functional properties. , 2015, Developmental and comparative immunology.

[16]  A. Summerfield,et al.  Comparative dendritic cell biology of veterinary mammals. , 2015, Annual review of animal biosciences.

[17]  M. Soller.  If a bull were a cow, how much milk would he give? , 2015, Annual review of animal biosciences.

[18]  L. Jouneau,et al.  Pig Skin Includes Dendritic Cell Subsets Transcriptomically Related to Human CD1a and CD14 Dendritic Cells Presenting Different Migrating Behaviors and T Cell Activation Capacities , 2014, The Journal of Immunology.

[19]  M. Beck,et al.  Characterization of the T-dependent antibody response (TDAR) to keyhole limpet hemocyanin (KLH) in the Göttingen minipig , 2014, Journal of Immunotoxicology.

[20]  M. Obradovic,et al.  Evidence for a common mucosal immune system in the pig☆ , 2014, Molecular Immunology.

[21]  Florent Ginhoux,et al.  Dendritic cells, monocytes and macrophages: a unified nomenclature based on ontogeny , 2014, Nature Reviews Immunology.

[22]  W. Gerner,et al.  CD2 and CD8α define porcine γδ T cells with distinct cytokine production profiles. , 2014, Developmental and comparative immunology.

[23]  Yasmine Belkaid,et al.  The Alarmin IL-33 Promotes Regulatory T Cell Function in the Intestine , 2014, Nature.

[24]  L. Ziegler‐Heitbrock,et al.  Monocyte subsets in man and other species. , 2014, Cellular immunology.

[25]  E. Shevach,et al.  tTregs, pTregs, and iTregs: similarities and differences , 2014, Immunological reviews.

[26]  V. Gerdts,et al.  The porcine innate immune system: An update , 2014, Developmental & Comparative Immunology.

[27]  T. K. van den Berg,et al.  The interaction between signal regulatory protein alpha (SIRPα) and CD47: structure, function, and therapeutic target. , 2014, Annual review of immunology.

[28]  Jean‐Pierre Amorij,et al.  Minipigs as an animal model for dermal vaccine delivery. , 2014, Comparative medicine.

[29]  Deepali Kumar,et al.  Clinical immune-monitoring strategies for predicting infection risk in solid organ transplantation , 2014, Clinical & translational immunology.

[30]  N. Cnubben,et al.  The minipig as an alternative non-rodent model for immunogenicity testing using the TNFα blockers adalimumab and infliximab , 2014, Journal of Immunotoxicology.

[31]  S. Heinritz,et al.  Use of pigs as a potential model for research into dietary modulation of the human gut microbiota , 2013, Nutrition Research Reviews.

[32]  J. Domínguez,et al.  Antigen targeting to APC: from mice to veterinary species. , 2013, Developmental and comparative immunology.

[33]  J. Estellé,et al.  The peripheral blood transcriptome reflects variations in immunity traits in swine: towards the identification of biomarkers , 2013, BMC Genomics.

[34]  Philippe Sanseau,et al.  Minipig and beagle animal model genomes aid species selection in pharmaceutical discovery and development. , 2013, Toxicology and applied pharmacology.

[35]  A. Archibald,et al.  Comparative Analysis of Monocyte Subsets in the Pig , 2013, The Journal of Immunology.

[36]  J. Harrow,et al.  Structural and functional annotation of the porcine immunome , 2013, BMC Genomics.

[37]  W. Gerner,et al.  Phenotypic maturation of porcine NK- and T-cell subsets. , 2013, Developmental and comparative immunology.

[38]  M. Sinkora,et al.  Different anti-CD21 antibodies can be used to discriminate developmentally and functionally different subsets of B lymphocytes in circulation of pigs. , 2013, Developmental and comparative immunology.

[39]  J. Leitner,et al.  CD27 expression discriminates porcine T helper cells with functionally distinct properties , 2013, Veterinary Research.

[40]  J. Holderness,et al.  Comparative biology of γδ T cell function in humans, mice, and domestic animals. , 2013, Annual review of animal biosciences.

[41]  N. Cnubben,et al.  The Göttingen minipig® as an alternative non-rodent species for immunogenicity testing: A demonstrator study using the IL-1 receptor antagonist anakinra , 2013, Journal of immunotoxicology.

[42]  M. Swindle,et al.  Animal models of toxicology testing: the role of pigs , 2013, Expert opinion on drug metabolism & toxicology.

[43]  F. Clubb,et al.  Swine as Models in Biomedical Research and Toxicology Testing , 2012, Veterinary pathology.

[44]  T. Singer,et al.  Minipig as a potential translatable model for monoclonal antibody pharmacokinetics after intravenous and subcutaneous administration , 2012, mAbs.

[45]  P. Haley.  The Immune System of Pigs: Structure and Function , 2011 .

[46]  H. Dawson.  A Comparative Assessment of the Pig, Mouse and Human Genomes: Structural and Functional Analysis of Genes Involved in Immunity and Inflammation , 2011 .

[47]  W. Harvey.  Regulatory Acceptance of the Minipig in Non-Pharmaceutical Industry and Research , 2011 .

[48]  N. Ganderup.  Adverse Responses to Drugs in Man: Critical Comparison of Reported Toxicological Findings in Minipigs and Humans , 2011 .

[49]  G. V. Mierlo,et al.  Immunotoxicology: Studies in the Minipig , 2011 .

[50]  Hans Nauwynck,et al.  The pig: a model for human infectious diseases , 2011, Trends in Microbiology.

[51]  R. Kapetanovic,et al.  The mononuclear phagocyte system of the pig as a model for understanding human innate immunity and disease , 2011, Journal of leukocyte biology.

[52]  J. Sims,et al.  The utility of the minipig as an animal model in regulatory toxicology. , 2010, Journal of pharmacological and toxicological methods.

[53]  L. Ellegaard,et al.  The RETHINK project--minipigs as models for the toxicity testing of new medicines and chemicals: an impact assessment. , 2010, Journal of pharmacological and toxicological methods.

[54]  M. Fredholm,et al.  The minipig as a platform for new technologies in toxicology. , 2010, Journal of pharmacological and toxicological methods.

[55]  Silvano Sozzani,et al.  Nomenclature of monocytes and dendritic cells in blood. , 2010, Blood.

[56]  K. Williams,et al.  Immunophenotyping of lymphocyte, monocyte and dendritic cell subsets in normal rhesus macaques by 12-color flow cytometry: clarification on DC heterogeneity. , 2010, Journal of immunological methods.

[57]  David R. Anderson,et al.  Acute Lymphoid and Gastrointestinal Toxicity Induced by Selective p38α Map Kinase and Map Kinase–Activated Protein Kinase-2 (MK2) Inhibitors in the Dog , 2010, Toxicologic pathology.

[58]  K. Williams,et al.  Evaluation of a 12‐color flow cytometry panel to study lymphocyte, monocyte, and dendritic cell subsets in humans , 2010, Cytometry. Part A : the journal of the International Society for Analytical Cytology.

[59]  Claudio Lottaz,et al.  Comparison of gene expression profiles between human and mouse monocyte subsets. , 2010, Blood.

[60]  H. Rothkötter.  Anatomical particularities of the porcine immune system--a physician's view. , 2009, Developmental and comparative immunology.

[61]  I. Kacskovics,et al.  Immunoglobulins, antibody repertoire and B cell development. , 2009, Developmental and comparative immunology.

[62]  W. Gerner,et al.  Porcine T lymphocytes and NK cells--an update. , 2009, Developmental and comparative immunology.

[63]  F. Blecha,et al.  Porcine host defense peptides: expanding repertoire and functions. , 2009, Developmental and comparative immunology.

[64]  J. Lunney,et al.  Molecular genetics of the swine major histocompatibility complex, the SLA complex. , 2009, Developmental and Comparative Immunology.

[65]  J. Lunney,et al.  The piglet as a model for B cell and immune system development , 2008, Veterinary Immunology and Immunopathology.

[66]  H. Salmon,et al.  Membrane markers of the immune cells in swine: an update. , 2008, Veterinary research.

[67]  K. McCullough,et al.  Targeting the porcine immune system—Particulate vaccines in the 21st century , 2008, Developmental & Comparative Immunology.

[68]  A. Archibald,et al.  Innate immune responses to replication of porcine reproductive and respiratory syndrome virus in isolated Swine alveolar macrophages. , 2007, Viral immunology.

[69]  P. Dash,et al.  Porcine γδ T cells: Possible roles on the innate and adaptive immune responses following virus infection , 2006 .

[70]  R. Haworth,et al.  Preclinical safety assessment of a DNA vaccine using particle-mediated epidermal delivery in domestic pig, minipig and mouse. , 2006, Experimental and toxicologic pathology : official journal of the Gesellschaft fur Toxikologische Pathologie.

[71]  V. Nogués,et al.  The minipig in dermatotoxicology: methods and challenges. , 2006, Experimental and toxicologic pathology : official journal of the Gesellschaft fur Toxikologische Pathologie.

[72]  S Beck,et al.  The genomic sequence and analysis of the swine major histocompatibility complex. , 2006, Genomics.

[73]  S. Gordon,et al.  Monocyte and macrophage heterogeneity , 2005, Nature Reviews Immunology.

[74]  J. Butler,et al.  Lymphocyte development in fetal piglets: facts and surprises. , 2005, Veterinary immunology and immunopathology.

[75]  J. Schölmerich,et al.  Immune status and risk for infection in patients receiving chronic immunosuppressive therapy. , 2005, The Journal of rheumatology.

[76]  W. Gerner,et al.  Intraepithelial but not lamina propria lymphocytes in the porcine gut are affected by dexamethasone treatment. , 2005, Veterinary immunology and immunopathology.

[77]  C. Hughes,et al.  Of Mice and Not Men: Differences between Mouse and Human Immunology , 2004, The Journal of Immunology.

[78]  Sang-Nae Cho,et al.  γδ T Cells in Immunity Induced by Mycobacterium bovis Bacillus Calmette-Guérin Vaccination , 2004, Infection and Immunity.

[79]  P. Bugelski,et al.  Predictive power of preclinical studies in animals for the immunogenicity of recombinant therapeutic proteins in humans. , 2004, Current opinion in molecular therapeutics.

[80]  L. Ziegler‐Heitbrock,et al.  Mechanism of glucocorticoid‐induced depletion of human CD14+CD16+ monocytes , 2003, Journal of leukocyte biology.

[81]  P. Haley.  Species differences in the structure and function of the immune system. , 2003, Toxicology.

[82]  R. Haworth,et al.  The Assessment of Local Tolerance, Acute Toxicity, and DNA Biodistribution Following Particle-Mediated Delivery of a DNA Vaccine to Minipigs , 2002, Toxicologic pathology.

[83]  M. Faldyna,et al.  Lymphocyte subsets in peripheral blood of dogs--a flow cytometric study. , 2001, Veterinary immunology and immunopathology.

[84]  Jishan Sun,et al.  Antibody repertoire development in fetal and newborn piglets, III. Colonization of the gastrointestinal tract selectively diversifies the preimmune repertoire in mucosal lymphoid tissues , 2000, Immunology.

[85]  J. Domínguez,et al.  Phenotypic characterization of monocyte subpopulations in the pig. , 2000, Immunobiology.

[86]  H. Yang,et al.  Phenotypic classification of porcine lymphocyte subpopulations in blood and lymphoid tissues , 1996, Immunology.

[87]  B. Cukrowska,et al.  Thymic B cells of pig fetuses and germ‐free pigs spontaneously produce IgM, IgG and IgA: detection by ELISPOT method , 1996, Immunology.

[88]  T. Flotte,et al.  Characterization of cutaneous antigen presentation in partially inbred miniature swine , 1994, Experimental dermatology.

[89]  F. Kovářů,et al.  Development of immune responses in early pig ontogeny. , 1994, Veterinary immunology and immunopathology.

[90]  D. Wesemann.  Microbes and B cell development. , 2015, Advances in immunology.

[91]  H. Kiyono,et al.  Terminology: nomenclature of mucosa-associated lymphoid tissue , 2008, Mucosal Immunology.

[92]  조상래.  γδ T Cells in Immunity Induced by Mycobacterium bovis Bacillus Calmette-Guérin Vaccination , 2004 .

[93]  P. Griebel,et al.  A road less travelled: large animal models in immunological research , 2003, Nature Reviews Immunology.

[94]  S. Jonjić,et al.  Simultaneous expression of CD4 and CD8 antigens by a substantial proportion of resting porcine T lymphocytes , 1987, European journal of immunology.