Immunology Letters 162 (2014) 1–2
Contents lists available at ScienceDirect
Immunology Letters journal homepage: www.elsevier.com/locate/immlet
Introduction to special issue on microbiome influences on host immunity
The paradigm of the germ theory disease has been one of the great achievements of medical science. However, its narrow focus on microbial pathogens did not consider the critical functions played by commensal microbiota in normal host physiology. Physicians have been liberally using antibiotics without considering potential consequences of these treatments on the immune system, energy metabolism, or neural development [1]. Immunologists also have considered the immune system mostly along militaristic lines, assuming that it exists solely for purposes of defense against the harsh world inhabited by microbial predators. Commensal microbes were considered to be either passive inhabitants of body surfaces or potentially pathogenic opportunists, and sometimes, as in the case of Ilya Metchnikoff, as relentless vermin that ultimately drove the aging process by their toxic excrement [2]. Today we recognize that microbiota are absolutely integral to host physiology. Immunologists now appreciate that microbiota directly defends the host against pathogens and it plays critical roles in the development of the host immune system. In turn, the host immune system does not merely fight pathogens that get through the body barrier defenses, but devotes substantial resources to shepherding the commensal microbiota to ensure its desirable composition and function. Bench immunologists can no longer ignore commensal microbiota in their experimental models. Having to account for this complex variable will undoubtedly create additional challenges and require a working knowledge of new technologies used to characterize microbiota and its functions. In this Special Issue on Microbiome Influences on Host Immunity we present a series of thoughtful reviews that explore the rapidly growing areas of investigation of host–microbiota interactions of particular interest to immunologists. Host recognition of the microbiota within the intestine is a crucial area of research and involves a combination of innate immune receptors and host IgA. Modulation of such recognition can lead to alterations in the microbiome and pathological outcomes. Ruth Ley and colleagues discuss the recognition of bacterial flora in the intestine with a focus on a single innate receptor, TLR5, which recognizes bacterial flagellin [3]. Charlotte Kaetzel provides an important overview of the regulation of IgA production and secretion by the intestinal flora and the importance of such sIgA production in breast milk [4]. Although most investigators study the interaction of host and microbiota in the context of the intestine, there are obviously http://dx.doi.org/10.1016/j.imlet.2014.08.006 0165-2478/© 2014 Elsevier B.V. All rights reserved.
important interactions elsewhere in the body and Massimo Costalonga reviews what is known about this subject in the oral cavity [5]. The induction of T cell-dependent antibody responses requires the involvement of a specialized subset of CD4 helper cells known as T follicular helper cells. Understanding how this cell population is regulated by the microbiota is therefore critical to develop a view of how antibody responses develop. Colleen Winstead reviews this important area and how Tfh cells are involved in maintaining the intestinal barrier [6]. Disruption of the normal microbiota can be harmful for the host and result in long-term inflammatory disease of the intestine. Andreas Baumler reviews the newly appreciated role of nutrient utilization in the intestine as an underlying cause of intestinal dysbiosis [7]. Such dysregulation of the intestinal microbiota can also influence inflammatory bowel disease and colorectal cancer. Christian Jobin discusses what we know about intestinal bacteria associated with the development of these diseases with a particular focus on Fusobacterium and Enterobacteriaceae [8]. Given the complexity of the intestinal microbiome, studying the role of intestinal bacteria in the incidence and progression of inflammatory bowel disease requires the examination of multiple parameters and the use of bioinformatics to make sense of these large data sets. Dan Knights reviews the application of “multi-omics” approaches in understanding the interaction of the microbiota and IBD [9]. In terms of clinical practice, a growing appreciation of the importance of the microbiota has led to the development of microbiota transplantation as a therapeutic approach. In fact, microbiota transplantation has a long history in veterinary and non-Western human medicine. Ed DePeters provides a historical and technical overview of the use of microbiota transplantation in the management of veterinary diseases [10]. Recently, this approach has also been increasingly used in patients suffering from refractory Clostridium difficile infection and there is hope that it may also have wider benefit in other disorders. Alexander Khoruts reviews this important area and discusses the potential and problems associated with fecal microbiota transplantation [11]. Our understanding of microbiota interaction with host immunity is growing exponentially as more basic science studies examine the importance of this issue in the development of normal and pathological immune responses. We are just beginning to appreciate how modulation of this interaction can be used therapeutically to influence disease states. It is hoped that these reviews will update
2
Introduction to special issue on microbiome influences on host immunity / Immunology Letters 162 (2014) 1–2
the reader and provide a useful launch pad for more research on this topic. References [1] Blaser MJ. Missing microbes: how the overuse of antibiotics is fueling our modern plagues. 1st ed. Henry Holt and Co; 2014. [2] Metchnikoff E, Mitchell PC. The prolongation of life: optimistic studies. London/New York: W. Heinemann/G.P. Putnam’s Sons; 1907. [3] Ley RE, Leifer CA, McConkey C, Li S, Chassaing B, Gewirtz AT. Linking genetic variation in human Toll-like receptor 5 genes to the gut microbiome’s potential to cause inflammation. Immunol Lett 2014 [in press]. [4] Kaetzel C. Cooperativity among secretory IgA, the polymeric immunoglobulin receptor, and the gut microbiota promotes host–microbial mutualism. Immunol Lett 2014, http://dx.doi.org/10.1016/j.imlet.2014.05.008. [5] Costalonga M, Herzberg M. The oral microbiome and the immunobiology of periodontal disease and caries. Immunol Lett 2014, http://dx.doi.org/ 10.1016/j.imlet.2014.08.017. [6] Winstead CJ. Follicular helper T cell-mediated mucosal barrier maintenance. Immunol Lett 2014, http://dx.doi.org/10.1016/j.imlet.2014.07.015. [7] Faber F, Baumler A. The impact of intestinal inflammation on the nutritional environment of the gut microbiota. Immunol Lett 2014, http://dx.doi.org/ 10.1016/j.imlet.2014.04.014. [8] Jobin C, Ellen-Vercoe E. Fusobacterium and Enterobacteriaceae: important players for CRC? Immunol Lett 2014, http://dx.doi.org/10.1016/j.imlet. 2014.05.014. [9] Knights D, Huang H, Vangay P, McKinlay CE. Multi-omics analysis of inflammatory bowel diseases. Immunol Lett 2014, http://dx.doi.org/ 10.1016/j.imlet.2014.07.014.
[10] DePeters E. Mini-review: rumen transfaunation. Immunol Lett 2014, http://dx.doi.org/10.1016/j.imlet.2014.05.009. [11] Khoruts A, Weingarden AR. Emergence of fecal microbiota transplantation as an approach to repair disrupted microbial gut ecology. Immunol Lett 2014, http://dx.doi.org/10.1016/j.imlet.2014.07.016.
Stephen J. McSorley (Ph.D.) ∗ Center for Comparative Medicine, Department of Anatomy, Physiology and Cell Biology, School of Veterinary Medicine, University of California Davis, Davis, CA 95616, USA Alexander Khoruts (MD) Division of Gastroenterology, Department of Medicine, Center for Immunology and BioTechnology Institute, University of Minnesota, Minneapolis, MN 55455, USA ∗ Corresponding author. E-mail addresses: [email protected] (S.J. McSorley), [email protected] (A. Khoruts).
Available online 12 August 2014
Contents lists available at ScienceDirect
Immunology Letters journal homepage: www.elsevier.com/locate/immlet
Introduction to special issue on microbiome influences on host immunity
The paradigm of the germ theory disease has been one of the great achievements of medical science. However, its narrow focus on microbial pathogens did not consider the critical functions played by commensal microbiota in normal host physiology. Physicians have been liberally using antibiotics without considering potential consequences of these treatments on the immune system, energy metabolism, or neural development [1]. Immunologists also have considered the immune system mostly along militaristic lines, assuming that it exists solely for purposes of defense against the harsh world inhabited by microbial predators. Commensal microbes were considered to be either passive inhabitants of body surfaces or potentially pathogenic opportunists, and sometimes, as in the case of Ilya Metchnikoff, as relentless vermin that ultimately drove the aging process by their toxic excrement [2]. Today we recognize that microbiota are absolutely integral to host physiology. Immunologists now appreciate that microbiota directly defends the host against pathogens and it plays critical roles in the development of the host immune system. In turn, the host immune system does not merely fight pathogens that get through the body barrier defenses, but devotes substantial resources to shepherding the commensal microbiota to ensure its desirable composition and function. Bench immunologists can no longer ignore commensal microbiota in their experimental models. Having to account for this complex variable will undoubtedly create additional challenges and require a working knowledge of new technologies used to characterize microbiota and its functions. In this Special Issue on Microbiome Influences on Host Immunity we present a series of thoughtful reviews that explore the rapidly growing areas of investigation of host–microbiota interactions of particular interest to immunologists. Host recognition of the microbiota within the intestine is a crucial area of research and involves a combination of innate immune receptors and host IgA. Modulation of such recognition can lead to alterations in the microbiome and pathological outcomes. Ruth Ley and colleagues discuss the recognition of bacterial flora in the intestine with a focus on a single innate receptor, TLR5, which recognizes bacterial flagellin [3]. Charlotte Kaetzel provides an important overview of the regulation of IgA production and secretion by the intestinal flora and the importance of such sIgA production in breast milk [4]. Although most investigators study the interaction of host and microbiota in the context of the intestine, there are obviously http://dx.doi.org/10.1016/j.imlet.2014.08.006 0165-2478/© 2014 Elsevier B.V. All rights reserved.
important interactions elsewhere in the body and Massimo Costalonga reviews what is known about this subject in the oral cavity [5]. The induction of T cell-dependent antibody responses requires the involvement of a specialized subset of CD4 helper cells known as T follicular helper cells. Understanding how this cell population is regulated by the microbiota is therefore critical to develop a view of how antibody responses develop. Colleen Winstead reviews this important area and how Tfh cells are involved in maintaining the intestinal barrier [6]. Disruption of the normal microbiota can be harmful for the host and result in long-term inflammatory disease of the intestine. Andreas Baumler reviews the newly appreciated role of nutrient utilization in the intestine as an underlying cause of intestinal dysbiosis [7]. Such dysregulation of the intestinal microbiota can also influence inflammatory bowel disease and colorectal cancer. Christian Jobin discusses what we know about intestinal bacteria associated with the development of these diseases with a particular focus on Fusobacterium and Enterobacteriaceae [8]. Given the complexity of the intestinal microbiome, studying the role of intestinal bacteria in the incidence and progression of inflammatory bowel disease requires the examination of multiple parameters and the use of bioinformatics to make sense of these large data sets. Dan Knights reviews the application of “multi-omics” approaches in understanding the interaction of the microbiota and IBD [9]. In terms of clinical practice, a growing appreciation of the importance of the microbiota has led to the development of microbiota transplantation as a therapeutic approach. In fact, microbiota transplantation has a long history in veterinary and non-Western human medicine. Ed DePeters provides a historical and technical overview of the use of microbiota transplantation in the management of veterinary diseases [10]. Recently, this approach has also been increasingly used in patients suffering from refractory Clostridium difficile infection and there is hope that it may also have wider benefit in other disorders. Alexander Khoruts reviews this important area and discusses the potential and problems associated with fecal microbiota transplantation [11]. Our understanding of microbiota interaction with host immunity is growing exponentially as more basic science studies examine the importance of this issue in the development of normal and pathological immune responses. We are just beginning to appreciate how modulation of this interaction can be used therapeutically to influence disease states. It is hoped that these reviews will update
2
Introduction to special issue on microbiome influences on host immunity / Immunology Letters 162 (2014) 1–2
the reader and provide a useful launch pad for more research on this topic. References [1] Blaser MJ. Missing microbes: how the overuse of antibiotics is fueling our modern plagues. 1st ed. Henry Holt and Co; 2014. [2] Metchnikoff E, Mitchell PC. The prolongation of life: optimistic studies. London/New York: W. Heinemann/G.P. Putnam’s Sons; 1907. [3] Ley RE, Leifer CA, McConkey C, Li S, Chassaing B, Gewirtz AT. Linking genetic variation in human Toll-like receptor 5 genes to the gut microbiome’s potential to cause inflammation. Immunol Lett 2014 [in press]. [4] Kaetzel C. Cooperativity among secretory IgA, the polymeric immunoglobulin receptor, and the gut microbiota promotes host–microbial mutualism. Immunol Lett 2014, http://dx.doi.org/10.1016/j.imlet.2014.05.008. [5] Costalonga M, Herzberg M. The oral microbiome and the immunobiology of periodontal disease and caries. Immunol Lett 2014, http://dx.doi.org/ 10.1016/j.imlet.2014.08.017. [6] Winstead CJ. Follicular helper T cell-mediated mucosal barrier maintenance. Immunol Lett 2014, http://dx.doi.org/10.1016/j.imlet.2014.07.015. [7] Faber F, Baumler A. The impact of intestinal inflammation on the nutritional environment of the gut microbiota. Immunol Lett 2014, http://dx.doi.org/ 10.1016/j.imlet.2014.04.014. [8] Jobin C, Ellen-Vercoe E. Fusobacterium and Enterobacteriaceae: important players for CRC? Immunol Lett 2014, http://dx.doi.org/10.1016/j.imlet. 2014.05.014. [9] Knights D, Huang H, Vangay P, McKinlay CE. Multi-omics analysis of inflammatory bowel diseases. Immunol Lett 2014, http://dx.doi.org/ 10.1016/j.imlet.2014.07.014.
[10] DePeters E. Mini-review: rumen transfaunation. Immunol Lett 2014, http://dx.doi.org/10.1016/j.imlet.2014.05.009. [11] Khoruts A, Weingarden AR. Emergence of fecal microbiota transplantation as an approach to repair disrupted microbial gut ecology. Immunol Lett 2014, http://dx.doi.org/10.1016/j.imlet.2014.07.016.
Stephen J. McSorley (Ph.D.) ∗ Center for Comparative Medicine, Department of Anatomy, Physiology and Cell Biology, School of Veterinary Medicine, University of California Davis, Davis, CA 95616, USA Alexander Khoruts (MD) Division of Gastroenterology, Department of Medicine, Center for Immunology and BioTechnology Institute, University of Minnesota, Minneapolis, MN 55455, USA ∗ Corresponding author. E-mail addresses: [email protected] (S.J. McSorley), [email protected] (A. Khoruts).
Available online 12 August 2014
