Condition-dependent alteration of cellular immunity by secondary symbionts in the pea aphid,Acyrthosiphon pisum

Endosymbionts can fundamentally alter host physiology. Whether such changes are beneficial or detrimental to one or both partners may depend on the dynamics of the symbiotic relationship. Here we investigate the relationship between facultative symbionts and host immune responses. The pea aphid, Acyrthosiphon pisum, maintains an obligate primary symbiont, but may also harbour one or more facultative, secondary symbionts. Given their more transient nature and relatively recent adoption of a symbiotic lifestyle compared to primary symbionts, secondary symbionts may present a challenge for the host immune system. We assessed the response of several key components of the cellular immune system (phenoloxidase activity, encapsulation, immune cell counts) in the presence of alternative secondary symbionts, investigating the role of host and secondary symbiont genotype in specific responses. There was no effect of secondary symbiont presence on the phenoloxidase response, but we found variation in the encapsulation response and in immune cell counts based largely on the secondary symbiont. Host genotype was less influential in determining immunity outcomes. Our results highlight the importance of secondary symbionts in shaping host immunity. Understanding the complex physiological responses that can be propagated by host-symbiont associations has important consequences for host ecology, including symbiont and pathogen transmission dynamics.     

Secretory autophagy of lysozyme in Paneth cells

Secretion of antimicrobial proteins is an important host defense mechanism against bacteria, yet how secretory cells maintain function during bacterial invasion has been unclear. We discovered that Paneth cells, specialized secretory cells in the small intestine, react to bacterial invasion by rerouting a critical secreted antibacterial protein through a macroautophagy/autophagy-based secretion system termed secretory autophagy. Mice harboring a mutation in an essential autophagy gene, a mutation which is common in Crohn disease patients, cannot reroute their antimicrobial cargo during bacterial invasion and thus have compromised innate immunity. We showed that this alternative secretion system is triggered by both a cell-intrinsic mechanism, involving the ER stress response, and a cell-extrinsic mechanism, involving subepithelial innate immune cells. Our findings uncover a new role for secretory autophagy in host defense and suggest how a mutation in an autophagy gene can predispose individuals to Crohn disease.     

The natural occurrence of secondary bacterial symbionts in aphids

1. Many insects host secondary bacterial symbionts that are known to have wide‐ranging effects on their hosts, from host‐plant use to resistance against natural enemies. This has been most widely studied in aphids, which have become a model system to study insect–bacteria interactions. 2. While there is an increasing understanding of the role of symbionts in aphids from controlled laboratory studies, we are only beginning to explore the impact of hosting these symbionts on eco‐evolutionary dynamics in natural systems. To date, many research groups have identified bacterial symbionts from various aphid species, providing us with a bank of literature on aphid–symbiont associations in natural populations. 3. The role of secondary symbionts in aphids is discussed, and the taxonomic and geographical distribution of symbionts among aphids are summarised, and the potential reasons for the patterns observed. The need to test for multiple symbiont species (and co‐infections) across many individuals and the whole distribution range of an aphid is highlighted, including sampling on all known host‐plant species. 4. It is further important also to consider variation within the symbiont, the aphid‐host and the surrounding community, e.g. host‐plants or the natural enemies, to understand how these have the potential to mediate aphid–symbiont interactions. 5. Finally, the knowledge gained from experimental work should now be used to understand the role of aphid secondary symbionts in field systems, to fully understand the potentially far‐reaching consequences of aphid endosymbionts on community and ecosystem processes.     

Bacterial Community Survey of Solenopsis invicta Buren (Red imported fire Ant) Colonies in the Presence and Absence of Solenopsis invicta Virus (SINV)

Insect bacterial symbionts contribute to many essential biological functions of their hosts and can also influence host fecundity and fitness. The physiological contribution symbionts provide can aid in immune response and xenobiotic detoxification. Both of these immune factors can directly impact strategies aimed at managing insect populations. One biological control strategy that shows promise in insects is the use of single-stranded RNA viruses within the group Dicistroviridae. The Solenopsis invicta Virus (SINV; Dicistroviridae), a ssRNA virus, has been proposed as a potential biological control agent for the urban pest S. invicta Buren or red imported fire ant (RIFA). SINV has been shown to be prevalent in RIFA populations of Texas and Florida; however, mortality is associated with high viral load. In other insect microbe systems, presence of particular bacteria induced resistance against Dicistrovirus. If this type of relationship is present in the RIFA–SINV system, their bacterial community could reduce the effectiveness of SINV as a biological control system. The advantage of 454 pyro-sequencing is that it enables classification of unculturable bacteria. This study examines the bacterial community in brood, workers, and reproductive cast members from colonies with and without SINV infection. Manipulation of the bacterial community may alter virus infection and replication within the mid-gut. Understanding the differences in the microbial community of ant colonies may provide insights that will refine current efforts designing control strategies for this important urban pest.     

Exposure to natural pathogens reveals costly aphid response to fungi but not bacteria

Immune responses are costly, causing trade‐offs between defense and other host life history traits. Aphids present a special system to explore the costs associated with immune activation since they are missing several humoral and cellular mechanisms thought important for microbial resistance, and it is unknown whether they have alternative, novel immune responses to deal with microbial threat. Here we expose pea aphids to an array of heat‐killed natural pathogens, which should stimulate immune responses without pathogen virulence, and measure changes in life‐history traits. We find significant reduction in lifetime fecundity upon exposure to two fungal pathogens, but not to two bacterial pathogens. This finding complements recent genomic and immunological studies indicating that pea aphids are missing mechanisms important for bacterial resistance, which may have important implications for how aphids interact with their beneficial bacterial symbionts. In general, recent exploration of the immune systems of non‐model invertebrates has called into question the generality of our current picture of insect immunity. Our data highlight that taking an ecological approach and measuring life‐history traits to a broad array of pathogens provides valuable information that can complement traditional approaches.     

Salmonella, the host and its microbiota

The intestine is host to a diverse bacterial community whose structure, at the phylum level, is maintained through unknown mechanisms. Acute inflammation triggered by enteric pathogens, such as Salmonella enterica serotype Typhimurium (S. Typhimurium), is accompanied by changes in the bacterial community structure marked by an outgrowth of the pathogen. Recent studies show that S. Typhimurium can harness benefit from the host response to edge out the beneficial bacterial species that dominate in the healthy gut. The elucidation of how S. Typhimurium alters the bacterial community structure during gastroenteritis is beginning to provide insights into mechanisms that dictate the balance between the host and its microbiota.     

Regulatory T Cells and Immune Tolerance in the Intestine

A fundamental role of the mammalian immune system is to eradicate pathogens while minimizing immunopathology. Instigating and maintaining immunological tolerance within the intestine represents a unique challenge to the mucosal immune system. Regulatory T cells are critical for continued immune tolerance in the intestine through active control of innate and adaptive immune responses. Dynamic adaptation of regulatory T-cell populations to the intestinal tissue microenvironment is key in this process. Here, we discuss specialization of regulatory T-cell responses in the intestine, and how a breakdown in these processes can lead to chronic intestinal inflammation.The mammalian host harbors a vast and diverse commensal microbiota. The gastrointestinal tract is a site of preferential colonization by commensal organisms, consisting of fungal, viral, and bacterial species. Initial microbial colonization of the host occurs during birth and continues until a stable commensal microbiota is established during childhood (Tannock 2007). Colonization of the gastrointestinal tract is a vital triggering stimuli for maturation of the mucosal immune system, and the presence of a commensal microbiota further benefits the host by providing resistance to invading pathogens and metabolism of dietary components (Macpherson et al. 2005; Hooper et al. 2012). A dynamic molecular dialogue between microbiota and host ensures this colonization occurs as a state of mutualism, the breakdown of which can result in chronic pathologies of the gastrointestinal tract, such as inflammatory bowel diseases (IBD) (Kaser et al. 2010; Maloy and Powrie 2011). Complex interactions between the microbiota, mucosal immune system, and the intestinal tissue cells provide multiple layers of regulation that control intestinal immunity. Here, we focus on the role of regulatory T cells as key components of intestinal homeostasis and discuss how tissue-specific adaptations contribute to their function when patrolling this challenging frontier.     

Patterns of environmental variability influence coral‐associated bacterial and algal communities on the Mesoamerican Barrier Reef

A coral's capacity to alter its microbial symbionts may enhance its fitness in the face of climate change. Recent work predicts exposure to high environmental variability may increase coral resilience and adaptability to future climate conditions. However, how this heightened environmental variability impacts coral‐associated microbial communities remains largely unexplored. Here, we examined the bacterial and algal symbionts associated with two coral species of the genus Siderastrea with distinct life history strategies from three reef sites on the Belize Mesoamerican Barrier Reef System with low or high environmental variability. Our results reveal bacterial community structure, as well as alpha‐ and beta‐diversity patterns, vary by host species. Differences in bacterial communities between host species were partially explained by high abundance of Deltaproteobacteria and Rhodospirillales and high bacterial diversity in Siderastrea radians. Our findings also suggest Siderastrea spp. have dynamic core bacterial communities that likely drive differences observed in the entire bacterial community, which may play a critical role in rapid acclimatization to environmental change. Unlike the bacterial community, Symbiodiniaceae composition was only distinct between host species at high thermal variability sites, suggesting that different factors shape bacterial versus algal communities within the coral holobiont. Our findings shed light on how domain‐specific shifts in dynamic microbiomes may allow for unique methods of enhanced host fitness.     

Diversity and stability of egg‐bacterial assemblages: The role of paternal care in the glassfrog Hyalinobatrachium colymbiphyllum

Embryos of oviparous organisms must cope with harsh environments and are especially susceptible to disease, considering that many immune mechanisms do not develop until later in life. Parents may transmit symbiotic microflora to eggs, which can contribute to embryo immune defense. Despite the importance of symbiotic microbes for immune function and survival of adult amphibians, vertical transfer of symbionts in amphibians has received less attention than in other taxa. Here, we test the role of male‐only parental care in establishing and maintaining the diversity of egg‐bacterial assemblages in a Neotropical glassfrog (Centrolenidae). Previous research suggests that father Hyalinobatrachium colymbiphyllum may transfer bacterial symbionts to their eggs. We combined a male‐removal experiment in situ with 16S rRNA gene amplicon sequencing to determine whether egg attendance by father H. colymbiphyllum influences the bacterial community and survival of eggs. We found that eggs harbor a diverse and stable bacterial assemblage. Despite different host environments, we found that adult skin and eggs supported very similar bacterial assemblages—even after removing fathers. While we found overlap in the bacteria present on eggs and their fathers, our experiment reveals that extended male care does not contribute to the maintenance of egg‐bacterial communities, so there may be other potential routes of transfer. This study contributes to our understanding of the diversity and maintenance of egg microbiomes, and motivates further research on how initial bacteria are acquired and the ontogenetic development of host–symbiont communities.     

Developmental symbiosis facilitates the multiple origins of herbivory

Developmental bias toward particular evolutionary trajectories can be facilitated through symbiosis. Organisms are holobionts, consisting of zygote‐derived cells and a consortia of microbes, and the development, physiology, and immunity of animals are properties of complex interactions between the zygote‐derived cells and microbial symbionts. Such symbionts can be agents of developmental plasticity, allowing an organism to develop in particular directions. This plasticity can lead to genetic assimilation either through the incorporation of microbial genes into host genomes or through the direct maternal transmission of the microbes. Such plasticity can lead to niche construction, enabling the microbes to remodel host anatomy and/or physiology. In this article, I will focus on the ability of symbionts to bias development toward the evolution of herbivory. I will posit that the behavioral and morphological manifestations of herbivorous phenotypes must be preceded by the successful establishment of a community of symbiotic microbes that can digest cell walls and detoxify plant poisons. The ability of holobionts to digest plant materials can range from being a plastic trait, dependent on the transient incorporation of environmental microbes, to becoming a heritable trait of the holobiont organism, transmitted through the maternal propagation of symbionts or their genes.     

Th17 Inflammation Model of Oropharyngeal Candidiasis in Immunodeficient Mice

Oropharyngeal Candidiasis (OPC) disease is caused not only due to the lack of host immune resistance, but also the absence of appropriate regulation of infection-induced immunopathology. Although Th17 cells are implicated in antifungal defense, their role in immunopathology is unclear. This study presents a method for establishing oral Th17 immunopathology associated with oral candidal infection in immunodeficient mice. The method is based on reconstituting lymphopenic mice with in vitro cultured Th17 cells, followed by oral infection with Candida albicans (C. albicans). Results show that unrestrained Th17 cells result in inflammation and pathology, and is associated with several measurable read-outs including weight loss, pro-inflammatory cytokine production, tongue histopathology and mortality, showing that this model may be valuable in studying OPC immunopathology. Adoptive transfer of regulatory cells (T_regs) controls and reduces the inflammatory response, showing that this model can be used to test new strategies to counteract oral inflammation. This model may also be applicable in studying oral Th17 immunopathology in general in the context of other oral diseases.     

Molecular interactions between bacterial symbionts and their hosts

Symbiotic bacteria are important in animal hosts, but have been largely overlooked as they have proved difficult to culture in the laboratory. Approaches such as comparative genomics and real-time PCR have provided insights into the molecular mechanisms that underpin symbiont-host interactions. Studies on the heritable symbionts of insects have yielded valuable information about how bacteria infect host cells, avoid immune responses, and manipulate host physiology. Furthermore, some symbionts use many of the same mechanisms as pathogens to infect hosts and evade immune responses. Here we discuss what is currently known about the interactions between bacterial symbionts and their hosts.     

Influence of the gastrointestinal microbiota on development of the immune system in young animals

The gastrointestinal tract (GIT) of adult mammals is colonized by a complex and dynamic community of microorganisms. Most protection against potential pathogens occurs via a mucosal immune system involving mechanisms of innate immunity as well as a secondary lymphoid organ, the gut-associated lymphoid tissue (GALT). However, the bacterial community also supports its host against invasion by potential pathogens, by a mechanism called 'colonization resistance'. Young animals need time to develop both a complex bacterial community and their immature GIT immune system, and until such developments have taken place, they are vulnerable to the presence of potential pathogens in their GIT. Initial protection against invading pathogens is provided by milk and colostrum, which contain antibodies and other bioactive components. At weaning, with the introduction of solid food and deprivation of the mother's milk, the young must also cope with a rapidly changing microbiota. The colonizing microbiota not only provides colonization resistance to potentially pathogenic bacteria. It also has a major role in the development of the intestinal immune system, both in terms of GALT development and mucosal immunity, and the induction of oral tolerance. Studies using gnotobiotic animal models have revealed that the presence of even limited numbers of the indigenous microbiota may influence the GIT immune system. Regulation of the composition of the GIT microbiota, e.g. by the use of pre- and probiotics, offers the possibility to influence the development of mucosal, and also systemic immunity.     

Type 3 regulatory T cells at the interface of symbiosis

The mammalian gastrointestinal tract accommodates trillions of bacteria, many of which provide beneficial effects to the host, including protection from pathogenic microorganisms and essential metabolites. However, the intestinal immune system needs to adapt to the constantly fluctuating microbial environment at mucosal surfaces in order to maintain homeostasis. In particular, the gut microbiota induces the differentiation of effector Th17 cells and regulatory T cells (Tregs) that express RORγt, the master regulator of antimicrobial type 3 immunity. RORγt⁺ Tregs constitute a major population of colonic Tregs that is distinct from thymusderived Tregs and require bacterial antigens for differentiation. The balance between Th17 cells and RORγt⁺ Tregs, that is, the tone of the local type 3 immune response, is regulated by the vitamin A metabolite retinoic acid produced by the host. Furthermore, Th17 cells and RORγt⁺ Tregs regulate intestinal type 2 immune responses, explaining how bacteria block allergic reactions. Here, we review the cellular and molecular mechanisms involved in the differentiation, regulation and function of RORγt⁺ (type 3) Tregs, and discuss the multiple equilibria that exist between effector T cells and Tregs, as well as between different types of immune responses, which are necessary to maintain homeostasis and health.     

The potential role of Th17 immune responses in coronavirus immunopathology and vaccine-induced immune enhancement

Increasing evidence points to host Th17 inflammatory responses as contributing to the severe lung pathology and mortality of lower respiratory tract infections from coronaviruses. This includes host inflammatory and cytokine responses to COVID-19 caused by the SARS-2 coronavirus (SARS CoV2). From studies conducted in laboratory animals, there are additional concerns about immune enhancement and the role of potential host immunopathology resulting from experimental human COVID-19 vaccines. Here we summarize evidence suggesting there may be partial overlap between the underlying immunopathologic processes linked to both coronavirus infection and vaccination, and a role for Th17 in immune enhancement and eosinophilic pulmonary immunopathology. Such findings help explain the link between viral-vectored coronavirus vaccines and immune enhancement and its reduction through alum adjuvants. Additional research may also clarify links between COVID-19 pulmonary immunopathology and heart disease.     

Insect Gut Symbiont Susceptibility to Host Antimicrobial Peptides Caused by Alteration of the Bacterial Cell Envelope

The molecular characterization of symbionts is pivotal for understanding the cross-talk between symbionts and hosts. In addition to valuable knowledge obtained from symbiont genomic studies, the biochemical characterization of symbionts is important to fully understand symbiotic interactions. The bean bug (Riptortus pedestris) has been recognized as a useful experimental insect gut symbiosis model system because of its cultivatable Burkholderia symbionts. This system is greatly advantageous because it allows the acquisition of a large quantity of homogeneous symbionts from the host midgut. Using these naïve gut symbionts, it is possible to directly compare in vivo symbiotic cells with in vitro cultured cells using biochemical approaches. With the goal of understanding molecular changes that occur in Burkholderia cells as they adapt to the Riptortus gut environment, we first elucidated that symbiotic Burkholderia cells are highly susceptible to purified Riptortus antimicrobial peptides. In search of the mechanisms of the increased immunosusceptibility of symbionts, we found striking differences in cell envelope structures between cultured and symbiotic Burkholderia cells. The bacterial lipopolysaccharide O antigen was absent from symbiotic cells examined by gel electrophoretic and mass spectrometric analyses, and their membranes were more sensitive to detergent lysis. These changes in the cell envelope were responsible for the increased susceptibility of the Burkholderia symbionts to host innate immunity. Our results suggest that the symbiotic interactions between the Riptortus host and Burkholderia gut symbionts induce bacterial cell envelope changes to achieve successful gut symbiosis.     

Symbiosis as the way of eukaryotic life: The dependent co-origination of the body

Molecular analyses of symbiotic relationships are challenging our biological definitions of individuality and supplanting them with a new notion of normal part–whole relationships. This new notion is that of a ‘holobiont’, a consortium of organisms that becomes a functionally integrated ‘whole’. This holobiont includes the zoological organism (the ‘animal’) as well as its persistent microbial symbionts. This new individuality is seen on anatomical and physiological levels, where a diversity of symbionts form a new ‘organ system’ within the zoological organism and become integrated into its metabolism and development. Moreover, as in normal development, there are reciprocal interactions between the ‘host’ organism and its symbionts that alter gene expression in both sets of cells. The immune system, instead of being seen as functioning solely to keep microbes out of the body, is also found to develop, in part, in dialogue with symbionts. Moreover, the immune system is actively involved in the colonization of the zoological organism, functioning as a mechanism for integrating microbes into the animal-cell community. Symbionts have also been found to constitute a second mode of genetic inheritance, providing selectable genetic variation for natural selection. We develop, grow and evolve as multi-genomic consortia/teams/ecosystems.     

Bacterial virulence, proinflammatory cytokines and host immunity: how to choose the appropriate Salmonella vaccine strain?

Salmonella infection in its mammalian host can be dissected into two main components. The co-ordinate expression of bacterial virulence genes which are designed to evade, subvert or circumvent the host response on the one hand, and the host defence mechanisms which are designed to restrict bacterial survival and replication on the other hand. The outcome of infection is determined by the one which succeeds in disturbing this equilibrium more efficiently. This delicate balance between Salmonella virulence and host immunity/inflammation has important implications for vaccine development or therapeutic intervention. Novel Salmonella vaccine candidates and live carriers for heterologous antigens are attenuated strains with defined genetic modifications of metabolic or virulence functions. Although genetic defects of different gene loci can lead to similar degrees of attenuation, effects on the course of infection may vary, thereby altering the quality of the elicited immune response. Studies with gene-deficient animals indicate that Salmonella typhimurium strains with mutations in aroA, phoP/phoQ or ssrA/ssrB invoke different immune responses and that a differential repertoire of pro-inflammatory cytokines is required for clearance. Consequently, Salmonella mutants defective in distinct virulence functions offer the potential to specifically modulate the immune response for defined medical applications.