Antigen presenting cells in mucosal sites of veterinary species

International audienceThe ability of antigen presenting cells, in particular dendritic cells, to integrate a variety of environmental signals, together with their ability to respond appropriately by initiating either tolerance or defensive immune responses make them cells of particular relevance and importance in the mucosal environment. They have been demonstrated in a variety of mucosal tissues in veterinary species and have been characterized to varying degrees, showing that fundamental immunological principles apply throughout all species, but also highlighting some species differences. A major advantage of carrying out immunological research in veterinary species is their size: it is possible to cannulate lymphatic ducts and obtain information about cell migration between different tissues. It is also possible to obtain pure populations of relatively rare cell types such as the plasmacytoid dendritic cells or mucosal dendritic cells ex vivo for the study of immune responses to diseases in their natural host and for other thorough functional studies. Two major myeloid antigen presenting cell (APC) (dendritic cells, DC) cell populations have been described in gut draining lymph and other mucosal sites in ruminants and pigs, characterised by the presence or absence of surface molecules, their enzyme profiles, their ability to phagocytose and their different potential as APC. There is evidence that one of these subsets has migrated from the diffuse mucosal tissue, where it is found as a phagocytic as well as stimulatory APC population, which in turn may be derived from blood macrophages. In addition, the presence and role in viral infection of the IFN-$\alpha$ producing plasmacytoid DC in mucosal tissue is discussed, based on studies in pigs

The postnatal development of the mucosal immune system and mucosal tolerance in domestic animals

The mucosal immune system is exposed to a range of antigens associated with pathogens, to which it must mount active immune responses. However, it is also exposed to a large number of harmless antigens associated with food and with commensal microbial flora, to which expression of active, inflammatory immune responses to these antigens is undesirable. The mucosal immune system must contain machinery capable of evaluating the antigens to which it is exposed and mounting appropriate effector or regulatory responses. Since the immune system is likely to have evolved initially in mucosal tissues, the requirement to prevent damaging allergic responses must be at least as old as the adaptive immune system, and studies of the mechanisms should include a range of non-mammalian species. Despite the importance for rational design of vaccines and for control of allergic reactions, the mechanisms involved are still largely unclear. It is not clear that the classical experimental protocol of “oral tolerance” is, in fact, measuring a biologically important phenomenon, nor is it clear whether tolerance is regulated in the evolutionarily recent organised lymphoid tissue (the lymph nodes) or the more ancient, diffuse architecture in the intestine. The capacity of the immune system to discriminate between “dangerous” and “harmless” antigens appears to develop with age and exposure to microbial flora. Thus, the ability of an individual or a group of animals to correctly regulate mucosal immune responses will depend on age, genetics and on their microbial environment and history. Attempts to manipulate the mucosal immune system towards active immune responses by oral vaccines, or towards oral tolerance, are likely to be confounded by environmentally-induced variability between individuals and between groups of animals

Antigen presenting cells in mucosal sites of veterinary species

The ability of antigen presenting cells, in particular dendritic cells, to integrate a variety of environmental signals, together with their ability to respond appropriately by initiating either tolerance or defensive immune responses make them cells of particular relevance and importance in the mucosal environment. They have been demonstrated in a variety of mucosal tissues in veterinary species and have been characterized to varying degrees, showing that fundamental immunological principles apply throughout all species, but also highlighting some species differences. A major advantage of carrying out immunological research in veterinary species is their size: it is possible to cannulate lymphatic ducts and obtain information about cell migration between different tissues. It is also possible to obtain pure populations of relatively rare cell types such as the plasmacytoid dendritic cells or mucosal dendritic cells ex vivo for the study of immune responses to diseases in their natural host and for other thorough functional studies. Two major myeloid antigen presenting cell (APC) (dendritic cells, DC) cell populations have been described in gut draining lymph and other mucosal sites in ruminants and pigs, characterised by the presence or absence of surface molecules, their enzyme profiles, their ability to phagocytose and their different potential as APC. There is evidence that one of these subsets has migrated from the diffuse mucosal tissue, where it is found as a phagocytic as well as stimulatory APC population, which in turn may be derived from blood macrophages. In addition, the presence and role in viral infection of the IFN-$\alpha$ producing plasmacytoid DC in mucosal tissue is discussed, based on studies in pigs

Foreword

The “raison d’être” for this special edition of Veterinary Research, entitled: Mucosal Immunology in Domestic Animals is two-fold: (1) A summary of the existing knowledge in the veterinary field is clearly useful for the rational design of mucosal vaccines and other aspects of animal health, with commercial and animal welfare implications. (2) However, it is also an attempt to illustrate the value of domestic animals in more fundamental aspects of mucosal immunological research. It is clear that the majority of foreign antigens are encountered via mucosal surfaces. This is true for harmless substances such as food and the huge mass of commensal bacteria. It is also true for the majority of pathogens, which frequently gain entry into the organism via the vast and relatively permeable mucosal tissues. However, the field of mucosal immunology is as yet relatively unexplored in comparison to the study of the systemic immune system, the traditional field of the immunologist working with rodents. Therefore, the classical questions for the mucosal immunologist: “How can the mucosal immune system discriminate between harmful and harmless antigens?” and: “How does it decide whether to mount appropriate defensive or tolerant responses?” are as yet only partially answered. Clearly, rodents have been and will remain the focus of scientific research, originally because of cost and ease of handling, now also because of the availability of transgenic animals and other research tools such as immunological reagents. However, their small body size makes them at best inconvenient and at worst impossible for such subject areas as cell migration, immune development and the study of relatively rare and inaccessible cells such as mucosal dendritic cells. There is also considerable evidence of immunological differences between species, and the study of a larger array of species, albeit mainly mammalian species as in this collection of reviews, can only contribute to a more fundamental understanding of immune mechanisms. Therefore, rather than looking at species differences as an obstacle in the path of our attempts to understand a functional immune system, we can turn this around and interpret it as an opportunity to broaden our understanding of the basic principles underlying immune mechanisms, as well as a chance to utilise different species for the study of different aspects of an immune function, always bearing in mind that species differences do exist. Apart from research based on our interest in such species as food sources or as our companions, veterinary species offer us the accessibility of rodents, the advantages of size of humans as well as their phylogenetic diversity for studies designed to complement the knowledge gained from the more traditional objects of our research. We hope that this volume of Veterinary Research demonstrates that this opportunity has already been grasped in the research carried out with veterinary species. The current issue includes reviews on many topics relevant to mucosal immunology: the anatomical features of the mucosal immune systems in several animal species, the dynamics of mucosae-derived immune cells, the innate and adaptive immune effector mechanisms at mucosal surfaces and the use of these concepts for the development of innovative mucosal vaccines. It only remains to thank all contributors for their hard and conscientious work and their willingness to throw a few novel and possibly controversial ideas into the arena

Foreword

The “raison d’être” for this special edition of Veterinary Research, entitled: Mucosal Immunology in Domestic Animals is two-fold: (1) A summary of the existing knowledge in the veterinary field is clearly useful for the rational design of mucosal vaccines and other aspects of animal health, with commercial and animal welfare implications. (2) However, it is also an attempt to illustrate the value of domestic animals in more fundamental aspects of mucosal immunological research. It is clear that the majority of foreign antigens are encountered via mucosal surfaces. This is true for harmless substances such as food and the huge mass of commensal bacteria. It is also true for the majority of pathogens, which frequently gain entry into the organism via the vast and relatively permeable mucosal tissues. However, the field of mucosal immunology is as yet relatively unexplored in comparison to the study of the systemic immune system, the traditional field of the immunologist working with rodents. Therefore, the classical questions for the mucosal immunologist: “How can the mucosal immune system discriminate between harmful and harmless antigens?” and: “How does it decide whether to mount appropriate defensive or tolerant responses?” are as yet only partially answered. Clearly, rodents have been and will remain the focus of scientific research, originally because of cost and ease of handling, now also because of the availability of transgenic animals and other research tools such as immunological reagents. However, their small body size makes them at best inconvenient and at worst impossible for such subject areas as cell migration, immune development and the study of relatively rare and inaccessible cells such as mucosal dendritic cells. There is also considerable evidence of immunological differences between species, and the study of a larger array of species, albeit mainly mammalian species as in this collection of reviews, can only contribute to a more fundamental understanding of immune mechanisms. Therefore, rather than looking at species differences as an obstacle in the path of our attempts to understand a functional immune system, we can turn this around and interpret it as an opportunity to broaden our understanding of the basic principles underlying immune mechanisms, as well as a chance to utilise different species for the study of different aspects of an immune function, always bearing in mind that species differences do exist. Apart from research based on our interest in such species as food sources or as our companions, veterinary species offer us the accessibility of rodents, the advantages of size of humans as well as their phylogenetic diversity for studies designed to complement the knowledge gained from the more traditional objects of our research. We hope that this volume of Veterinary Research demonstrates that this opportunity has already been grasped in the research carried out with veterinary species. The current issue includes reviews on many topics relevant to mucosal immunology: the anatomical features of the mucosal immune systems in several animal species, the dynamics of mucosae-derived immune cells, the innate and adaptive immune effector mechanisms at mucosal surfaces and the use of these concepts for the development of innovative mucosal vaccines. It only remains to thank all contributors for their hard and conscientious work and their willingness to throw a few novel and possibly controversial ideas into the arena

An ex-vivo model for reperfusion of laryngotracheal grafts

OBJECTIVE: To describe the development of an ex vivo model to facilitate the study of ischemia-reperfusion injury in laryngotracheal grafts taken from Minnesota minipigs. STUDY DESIGN: This is a descriptive study. METHODS: Laryngotracheal grafts from Minnesota minipigs were harvested and placed in cold storage for 3 hours. Autologous blood was used to reperfuse the graft for up to 8 hours using the described reperfusion model. RESULTS: By altering retrieval technique and pressures within the graft, we demonstrated healthy grafts after 8 hours of reperfusion. CONCLUSIONS: Ex vivo reperfusion offers a range of experimental advantages over in vivo reperfusion including close control of interventions, ease of outcome measurement, and reduction in animal use. This model is now ready to be used for further studies of interventions to reduce ischemia-reperfusion injury in these grafts

Effects of Infection with Transmissible Gastroenteritis Virus on Concomitant Immune Responses to Dietary and Injected Antigens

Normal piglets weaned onto soy- or egg-based diets generated antibody responses to fed protein. Concurrent infection with transmissible gastroenteritis virus (TGEV) did not affect the responses to dietary antigens at weaning, nor did it affect the subsequent development of tolerance. However, TGEV infection did enhance the primary immunoglobulin M (IgM) and IgG1, but not IgG2, antibody responses to injected soy in comparison to those of uninfected animals. Paradoxically, TGEV-infected animals showed an enhanced primary IgG1 antibody response to injected soy at 4 weeks of age, but they subsequently showed a reduced secondary response after an intraperitoneal challenge at 9 weeks of age in comparison to uninfected animals. The results suggest that an enteric virus, either used as a vaccine vector or present as a subclinical infection, may not have significant effects on the development of dietary allergies but may have effects both on the primary response and on the subsequent recall response to systemic antigens to which the animal is exposed concurrently with virus antigens