Role of IgA in the early-life establishment of the gut microbiota and immunity: Implications for constructing a healthy start.

Colonization and maturation of the gut microbiota (GM) during early life is a landmark event that fundamentally influences the (early) immunity and later-life health of various mammals. This is a delicate, systematic process that is biologically actively regulated by infants and their mothers, where (secretory) IgA, an important regulator of microbes found in breast milk and generated actively by infants, may play a key role. By binding to microbes, IgA can inhibit or enhance their colonization, influence their gene expression, and regulate immune responses. IgA dysfunction during early life is associated with disrupted GM maturation and various microbe-related diseases, such as necrotizing enterocolitis and diarrhea, which can also have a lasting effect on GM and host health. This review discusses the process of early GM maturation and its interaction with immunity and the role of IgA (focusing on milk secretory IgA) in regulating this process. The possible application of this knowledge in promoting normal GM maturation processes and immune education has also been highlighted.

MgrA Activates Staphylococcal Capsule via SigA-Dependent Promoter.

Staphylococcus aureus capsule polysaccharide is an important antiphagocytic virulence factor. The cap genes are regulated at the promoter element (Pcap) upstream of the cap operon. Pcap, which consists of a dominant SigB-dependent promoter and a weaker upstream SigA-dependent promoter, is activated by global regulator MgrA. How MgrA activates capsule is unclear. Here, we showed that MgrA directly bound to the Pcap region and affected the SigA-dependent promoter. Interestingly, an electrophoretic mobility shift assay showed that MgrA bound to a large region of Pcap, mainly downstream of the SigA-dependent promoter. We further showed that the ArlRS two-component system and the Agr quorum sensing system activated capsule primarily through MgrA in the early growth phases.IMPORTANCE The virulence of Staphylococcus aureus depends on the expression of various virulence factors, which is governed by a complex regulatory network. We have been using capsule as a model virulence factor to study virulence gene regulation in S. aureus MgrA is one of the regulators of capsule and has a major effect on capsule production. However, how MgrA regulates capsule genes is not understood. In this study, we were able to define the mechanism involving MgrA regulation of capsule. In addition, we also delineated the role of MgrA in capsule regulatory pathways involving the key virulence regulators Agr and Arl. This study further advances our understanding of virulence gene regulation in S. aureus, an important human pathogen.

Current understanding of the gut microbiota shaping mechanisms.

Increasing evidences have shown strong associations between gut microbiota and many human diseases, and understanding the dynamic crosstalks of host-microbe interaction in the gut has become necessary for the detection, prevention, or therapy of diseases. Many reports have showed that diet, nutrient, pharmacologic factors and many other stimuli play dominant roles in the modulation of gut microbial compositions. However, it is inappropriate to neglect the impact of host factors on shaping the gut microbiota. In this review, we highlighted the current findings of the host factors that could modulate the gut microbiota. Particularly the epithelium-associated factors, including the innate immune sensors, anti-microbial peptides, mucus barrier, secretory IgAs, epithelial microvilli, epithelial tight junctions, epithelium metabolism, oxygen barrier, and even the microRNAs are discussed in the context of the microbiota shaping. With these shaping factors, the gut epithelial cells could select the residing microbes and affect the microbial composition. This knowledge not only could provide the opportunities to better control many diseases, but may also be used for predicting the success of fecal microbiota transplantation clinically.

IgA tetramerization improves target breadth but not peak potency of functionality of anti-influenza virus broadly neutralizing antibody.

Mucosal immunoglobulins comprise mainly secretory IgA antibodies (SIgAs), which are the major contributor to pathogen-specific immune responses in mucosal tissues. These SIgAs are highly heterogeneous in terms of their quaternary structure. A recent report shows that the polymerization status of SIgA defines their functionality in the human upper respiratory mucosa. Higher order polymerization of SIgA (i.e., tetramers) leads to a marked increase in neutralizing activity against influenza viruses. However, the precise molecular mechanisms underlying the effects of SIgA polymerization remain elusive. Here, we developed a method for generating recombinant tetrameric monoclonal SIgAs. We then compared the anti-viral activities of these tetrameric SIgAs, which possessed variable regions identical to that of a broadly neutralizing anti-influenza antibody F045-092 against influenza A viruses, with that of monomeric IgG or IgA. The tetrameric SIgA showed anti-viral inhibitory activity superior to that of other forms only when the antibody exhibits low-affinity binding to the target. By contrast, SIgA tetramerization did not substantially modify anti-viral activity against targets with high-affinity binding. Taken together, the data suggest that tetramerization of SIgA improved target breadth, but not peak potency of antiviral functions of the broadly neutralizing anti-influenza antibody. This phenomenon presumably represents one of the mechanisms by which SIgAs present in human respiratory mucosa prevent infection by antigen-drifted influenza viruses. Understanding the mechanisms involved in cross neutralization of viruses by SIgAs might facilitate the development of vaccine strategies against viral infection of mucosal tissues.

La génétique de l'hôte influe sur les écosystèmes microbiens par l'intermédiaire du système immunitaire de l'hôte.

Genetic evolution of multicellular organisms occurred as a response to environmental challenges, in particular competition for nutrients, climatic change, physical and chemical stressors and pathogens. However organism fitness depends on both the efficiency of its defences and its capacities for benefiting from its symbiotic organisms. Indeed microbes not only engender pathogenies, but enable efficient uptake of host non-self biodegradable nutriments. Furthermore, microbes play an important role in the development of host immunity. We shall review here the associations between some specific genes of the host, microbiota and the immune system. Recent genome-wide association studies disclose that symbiosis between host and microbiota results from a stringent genetic co-evolution. On the other hand, a microbe subset isolated from murine and human microbiotes has been identified on the basis of its interaction with both the host genetics and immunity. Remarkably, microbes which have two such connections are taxonomically related. The best performing bacterial genuses in these two perspectives are Bifidobacterium, Lactobacillus and Akkermansia. We conclude that future therapies targeting microbiota within the framework of chronic inflammatory diseases must consider together host immune and genetic characters associated with microbiota homeostasis.

Recombinant IgA production for mucosal passive immunization, advancing beyond the hurdles.

Vaccination is a successful strategy to proactively develop immunity to a certain pathogen, but most vaccines fail to trigger a specific immune response at the mucosal surfaces, which are the first port of entry for infectious agents. At the mucosal surfaces, the predominant immunoglobulin is secretory IgA (SIgA) that specifically neutralizes viruses and prevents bacterial colonization. Mucosal passive immunization, i.e. the application of pathogen-specific SIgAs at the mucosae, can be an effective alternative to achieve mucosal protection. However, this approach is not straightforward, mainly because SIgAs are difficult to obtain from convalescent sources, while recombinant SIgA production is challenging due to its complex structure. This review provides an overview of manufacturing difficulties presented by the unique structural diversity of SIgAs, and the innovative solutions being explored for SIgA production in mammalian and plant expression systems.

Mucosal and systemic immune responses induced by a single time vaccination strategy in mice.

Vaccination is considered by the World Health Organization as the most cost-effective strategy for controlling infectious diseases. In spite of great successes with vaccines, many infectious diseases are still leading killers, because of the inadequate coverage of many vaccines. Several factors have been responsible: number of doses, high vaccine reactogenicity, vaccine costs, vaccination policy, among others. Contradictorily, few vaccines are of single dose and even less of mucosal administration. However, more common infections occur via mucosa, where secretory immunoglobulin A plays an essential role. As an alternative, we proposed a novel protocol of vaccination called Single Time Vaccination Strategy (SinTimVaS) by immunizing 2 priming doses at the same time: one by mucosal route and the other by parenteral route. Here, the mucosal and systemic responses induced by Finlay adjuvants (AF Proteoliposome 1 and AF Cochleate 1) implementing SinTimVaS in BALB/c mice were evaluated. One intranasal dose of AF Cochleate 1 and an intramuscular dose of AF Proteoliposome 1 adsorbed onto aluminum hydroxide, with bovine serum albumin or tetanus toxoid as model antigens, administrated at the same time, induced potent specific mucosal and systemic immune responses. Also, we demonstrated that SinTimVaS using other mucosal routes like oral and sublingual, in combination with the subcutaneous route elicits immune responses. SinTimVaS, as a new immunization strategy, could increase vaccination coverage and reduce time-cost vaccines campaigns, adding the benefits of immune response in mucosa.

Modeling of Virion Collisions in Cervicovaginal Mucus Reveals Limits on Agglutination as the Protective Mechanism of Secretory Immunoglobulin A.

Secretory immunoglobulin A (sIgA), a dimeric antibody found in high quantities in the gastrointestinal mucosa, is broadly associated with mucosal immune protection. A distinguishing feature of sIgA is its ability to crosslink pathogens, thereby creating pathogen/sIgA aggregates that are too large to traverse the dense matrix of mucin fibers in mucus layers overlying epithelial cells and consequently reducing infectivity. Here, we use modeling to investigate this mechanism of "immune exclusion" based on sIgA-mediated agglutination, in particular the potential use of sIgA to agglutinate HIV in cervicovaginal mucus (CVM) and prevent HIV transmission. Utilizing reported data on HIV diffusion in CVM and semen, we simulate HIV collision kinetics in physiologically-thick mucus layers-a necessary first step for sIgA-induced aggregation. We find that even at the median HIV load in semen of acutely infected individuals possessing high viral titers, over 99% of HIV virions will penetrate CVM and reach the vaginal epithelium without colliding with another virion. These findings imply that agglutination is unlikely to be the dominant mechanism of sIgA-mediated protection against HIV or other sexually transmitted pathogens. Rather, we surmise that agglutination is most effective against pathogens either present at exceedingly high concentrations or that possess motility mechanisms other than Brownian diffusion that significantly enhance encounter rates.

Mucosal Immunosenescence in the Gastrointestinal Tract: A Mini-Review.

It has been shown that pathogen-specific secretory IgA (SIgA) antibody (Ab) is the major player at mucosal surfaces for host defense. However, alterations in the mucosal immune system occur in advanced aging, which results in a failure of induction of SIgA Abs for the protection from infectious diseases. Signs of mucosal senescence first appear in the gut immune system. Further, changes in the intestinal microbiota most likely influence mucosal immunity. To overcome the immunological aging decline in mucosal immunity, several adjuvant systems including mucosal dendritic cell targeting have been shown to be attractive and effective immunological strategies. Similarly, microfold (M) cells involved in the antigen (Ag) uptake are ideal targets for facilitating Ag-specific mucosal immune responses. However, the numbers of M cells are reduced in aged mice. In this regard, Spi-B, an essential transcription factor for the functional and structural differentiation of M cells, could be a potent strategy for the induction of effective mucosal immunity in aging.

IgA, IgA receptors, and their anti-inflammatory properties.

Immunoglobulin A (IgA) is the most abundantly produced antibody isotype in mammals. The primary function of IgA is to maintain homeostasis at mucosal surfaces and play a role in immune protection. IgA functions mainly through interaction with multiple receptors including IgA Fc receptor I (FcαRI), transferrin receptor 1 (CD71), asialoglycoprotein receptor (ASGPR), Fcα/µR, FcRL4, and DC-SIGN/SIGNR1. In this review we discuss recent data demonstrating anti-inflammatory functions of IgA through two receptors, the FcαRI and DC-SIGN/SIGNR1 interactions in the regulation of immunity. Serum monomeric IgA is able to mediate an inhibitory signal following the interaction with FcαRI. It results in partial phosphorylation of its FcRγ-ITAM and the recruitment of the tyrosine phosphatase SHP-1, which induces cell inhibition following the formation of intracellular clusters named inhibisomes. In contrast, cross-linking of FcαRI by multimeric ligands induces a full phosphorylation of the FcRγ-ITAM leading to the recruitment of the tyrosine kinase Syk and cell activation. In addition, secretory IgA can mediate a potent anti-inflammatory function following the sugar-dependent interaction with SIGNR1 on dendritic cells which induces an immune tolerance via regulatory T cell expansion. Overall, the anti-inflammatory effect of serum and secretory IgA plays a crucial role in the physiology and in the prevention of tissue damage in multiple autoimmune and inflammatory diseases.

Salivary pellicles on titanium and their effect on metabolic activity in Streptococcus oralis.

BACKGROUND: Titanium implants in the oral cavity are covered with a saliva-derived pellicle to which early colonizing microorganisms such as Streptococcus oralis can bind. The protein profiles of salivary pellicles on titanium have not been well characterized and the proteins of importance for binding are thus unknown. Biofilm bacteria exhibit different phenotypes from their planktonic counterparts and contact with salivary proteins may be one factor contributing to the induction of changes in physiology. We have characterized salivary pellicles from titanium surfaces and investigated how contact with uncoated and saliva-coated titanium surfaces affects metabolic activity in adherent cells of S. oralis. METHODS: Salivary pellicles on smooth titanium surfaces were desorbed and these, as well as purified human saliva, were subjected to two-dimensional gel electrophoresis and mass spectroscopy. A parallel plate flow-cell model was used to study binding of a fresh isolate of S. oralis to uncoated and saliva-coated titanium surfaces. Metabolic activity was assessed using the BacLight CTC Vitality Kit and confocal scanning laser microscopy. Experiments were carried out in triplicate and the results analyzed using Student's t-test or ANOVA. RESULTS: Secretory IgA, α-amylase and cystatins were identified as dominant proteins in the salivary pellicles. Selective adsorption of proteins was demonstrated by the enrichment of prolactin-inducible protein and absence of zinc-α2-glycoprotein relative to saliva. Adherence of S. oralis to titanium led to an up-regulation of metabolic activity in the population after 2 hours. In the presence of a salivary pellicle, this effect was enhanced and sustained over the following 22 hour period. CONCLUSIONS: We have shown that adherence to smooth titanium surfaces under flow causes an up-regulation of metabolic activity in the early oral colonizer S. oralis, most likely as part of an adaptation to the biofilm mode of life. The effect was enhanced by a salivary pellicle containing sIgA, α-amylase, cystatins and prolactin-inducible protein which was, for the first time, identified as an abundant component of salivary pellicles on titanium. Further studies are needed to clarify the mechanisms underlying the effect of surface contact on metabolic activity as well as to identify the salivary proteins responsible for enhancing the effect.

Effort-reward imbalance at work and pre-clinical biological indices of ill-health: the case for salivary immunoglobulin A.

Physiological indices of stress and ill-health (cortisol and salivary immunoglobulin A) were assessed to determine if they were predicted by Siegrist's effort-reward imbalance model (ERI) with an aim of identifying employees at risk of illness. Male Australian dairy farmers (N=66) completed the Perceived Stress Scale, Work related Questions II & III, Eysenck Personality Questionnaire Revised--Short and demographic questions and provided morning saliva samples (at awakening and 30 min post awakening) on a working day, which were subsequently analysed for cortisol and salivary immunoglobulin A (sIgA) concentration levels. A high percentage (45.5%) of the sample reported an imbalance between efforts and rewards in the workplace that may place them 'at risk' for ill-health. After controlling for disposition, sIgA scores were more successfully predicted by the ERI than the cortisol assessments. Although both efforts and rewards were significantly associated with sIgA, efforts were most strongly associated. The dispositional trait overcommitment, did not moderate the experience of stress on the physiologic indices. The current investigation supports the continued use of sIgA in studies that use biomarkers to assess occupational stress. ERI ratio scores >1 aligned with previous findings that suggest elevated risk of illness for these employees.

Células dendríticas del intestino humano como controladoras de la inmunidad mucosa / Human intestinal dendritic cells as controllers of mucosal immunity

Las células dendríticas son las células profesionales presentadoras de antígenos más potentes que existen y, tras realizar la presentación antigénica, controlan el tipo de respuesta inmune que se establecerá (proinflamatoria/reguladora), así como su localización. Debido a su gran plasticidad y capacidad de maduración en respuesta a señales de peligro locales derivadas de la inmunidad innata, las células dendríticas son un elemento clave en la conexión entre la inmunidad innata y las respuestas de la inmunidad adaptativa. En el intestino, las células dendríticas controlan los mecanismos de la tolerancia inmunológica frente a los antígenos de la dieta y/o la flora comensal, a la vez que son capaces de iniciar una respuesta inmunológica activa en presencia de un patógeno invasor. Las células dendríticas son pues muy eficientes en controlar el delicado balance entre tolerancia/inmunidad en un ambiente tan cargado de antígenos como es el intestino, y cualquier factor que las afecte puede tener repercusiones en su funcionalidad, pudiendo en última instancia desarrollarse patologías intestinales como la enfermedad celiaca o las enfermedades inflamatorias intestinales. En esta revisión sintetizaremos nuestro conocimiento de las células dendríticas del intestino humano, su capacidad para expresar e inducir marcadores de migración, los diversos factores ambientales que modulan sus propiedades, los diferentes subtipos de células dendríticas que nos encontramos en el intestino y los problemas derivados de su estudio incluyendo sus diferentes estrategias de identificación, las diferencias entre humanos y modelos murinos y sus variaciones fenotípicas a lo largo del tracto gastrointestinal (AU)

Dendritic cells are the most potent, professional antigen-presenting cells in the body; following antigen presentation they control the type (proinflammatory/regulatory) of immune response that will take place, as well as its location. Given their high plasticity and maturation ability in response to local danger signals derived from innate immunity, dendritic cells are key actors in the connection between innate immunity and adaptive immunity responses. In the gut dendritic cells control immune tolerance mechanisms against food and/or commensal flora antigens, and are also capable of initiating an active immune response in the presence of invading pathogens. Dendritic cells are thus highly efficient in controlling the delicate balance between tolerance and immunity in an environment so rich in antigens as the gut, and any factor involving these cells may impact their function, ultimately leading to the development of bowel conditions such as celiac disease or inflammatory bowel disease. In this review we shall summarize our understanding of human intestinal dendritic cells, their ability to express and induce migration markers, the various environmental factors modulating their properties, their subsets in the gut, and the problems entailed by their study, including identification strategies, differences between humans and murine models, and phenotypical variations along the gastrointestinal tract (AU)

A combination of Flt3 ligand cDNA and CpG oligodeoxynucleotide as nasal adjuvant elicits protective secretory-IgA immunity to Streptococcus pneumoniae in aged mice.

Our previous study showed that a combination of a plasmid-expressing Flt3 ligand (pFL) and CpG oligodeoxynucleotides (CpG ODN) as a combined nasal adjuvant elicited mucosal immune responses in aged (2-y-old) mice. In this study, we investigated whether a combination of pFL and CpG ODN as a nasal adjuvant for a pneumococcal surface protein A (PspA) would enhance PspA-specific secretory-IgA Ab responses, which could provide protective mucosal immunity against Streptococcus pneumoniae infection in aged mice. Nasal immunization with PspA plus a combination of pFL and CpG ODN elicited elevated levels of PspA-specific secretory-IgA Ab responses in external secretions and plasma in both young adult and aged mice. Significant levels of PspA-specific CD4(+) T cell proliferative and PspA-induced Th1- and Th2- type cytokine responses were noted in nasopharyngeal-associated lymphoreticular tissue, cervical lymph nodes, and spleen of aged mice, which were equivalent to those in young adult mice. Additionally, increased numbers of mature-type CD8, CD11b-expressing dendritic cells were detected in mucosal inductive and effector lymphoid tissues of aged mice. Importantly, aged mice given PspA plus a combination of pFL and CpG ODN showed protective immunity against nasal S. pneumoniae colonization. These results demonstrate that nasal delivery of a combined DNA adjuvant offers an attractive possibility for protection against S. pneumoniae in the elderly.

A intervenção de enfermagem: relaxamento e seus efeitos no sistema imunológico de puérperas / A nursing intervention relaxation, and its effects on the immune system of postpartum women

OBJETIVOS: Avaliar os efeitos da técnica de relaxamento nos níveis de Imunoglobulina A (IgA) salivar em puérperas e a relação com as variáveis: idade, grau de instrução, estado civil, tipo de parto e paridade. MÉTODOS: Estudo experimental randomizado realizado em uma maternidade do Espírito Santo (Brasil). A amostra constituiu-se de 60 puérperas. O grupo experimental composto por 30 puérpuras seguiu a técnica de relaxamento proposta por Benson. As variáveis foram coletadas por meio de formulário específico e o nível de IgA salivar por imunoturbidimetria em dois momentos: até 24 horas pós-parto e 7 dias depois. RESULTADOS: Verificou-se aumento significativo dos níveis de IgA no grupo experimental (p= 0,01) após a prática do relaxamento e ausência de relação entre as variáveis de controle e a IgA. CONCLUSÃO: O relaxamento pode ajudar a aumentar a resistência imunológica de puérperas.

OBJECTIVES: To evaluate the effects of relaxation techniques in the levels of immunoglobulin A (IgA) in saliva of postpartum women, in relationship to the variables: age, education level, marital status, type of delivery and parity. METHODS: This experimental, randomized trial was conducted in a maternity ward of Espirito Santo (Brazil). The sample consisted of 60 postpartum women. The experimental group consisted of 30 postpartum women who received the relaxation technique proposed by Benson. The levels were collected using a specific form and level of salivary IgA by immunoturbidimetry in two stages: up to 24 hours postpartum, and 7 days later. RESULTS: We observed a significant increase of IgA levels in the experimental group (p = 0.01) after the practice of relaxation, and a lack of relationship between the control variables and IgA. CONCLUSIONS: Relaxation can help increase immunological resistance in postpartum women.

OBJETIVOS: Evaluar los efectos de la técnica de relajación en los niveles de Inmunoglobulina A (IgA) salival en puérperas y la relación con las variables: edad, grado de instrucción, estado civil, tipo de parto y paridad. MÉTODOS: Estudio experimental randomizado realizado en una maternidad de Espírito Santo (Brasil).La muestra se constituyó de 60 puérperas. El grupo experimental compuesto por 30 puérperas siguió la técnica de relajación propuesta por Benson. Las variables fueron recolectadas por medio de un formulario específico y el nivel de IgA salival por imunoturbidimetria en dos momentos: hasta 24 horas post-parto y 7 días después. RESULTADOS: Se verificó aumento significativo de los niveles de IgA en el grupo experimental (p= 0,01) después de la práctica de relajación y ausencia de relación entre las variables de control y la IgA. CONCLUSIÓN: La relajación puede ayudar a aumentar la resistencia inmunológica de puérperas.

The microbiota mediates pathogen clearance from the gut lumen after non-typhoidal Salmonella diarrhea.

Many enteropathogenic bacteria target the mammalian gut. The mechanisms protecting the host from infection are poorly understood. We have studied the protective functions of secretory antibodies (sIgA) and the microbiota, using a mouse model for S. typhimurium diarrhea. This pathogen is a common cause of diarrhea in humans world-wide. S. typhimurium (S. tm(att), sseD) causes a self-limiting gut infection in streptomycin-treated mice. After 40 days, all animals had overcome the disease, developed a sIgA response, and most had cleared the pathogen from the gut lumen. sIgA limited pathogen access to the mucosal surface and protected from gut inflammation in challenge infections. This protection was O-antigen specific, as demonstrated with pathogens lacking the S. typhimurium O-antigen (wbaP, S. enteritidis) and sIgA-deficient mice (TCRß(-/-)δ(-/-), J(H) (-/-), IgA(-/-), pIgR(-/-)). Surprisingly, sIgA-deficiency did not affect the kinetics of pathogen clearance from the gut lumen. Instead, this was mediated by the microbiota. This was confirmed using 'L-mice' which harbor a low complexity gut flora, lack colonization resistance and develop a normal sIgA response, but fail to clear S. tm(att) from the gut lumen. In these mice, pathogen clearance was achieved by transferring a normal complex microbiota. Thus, besides colonization resistance ( = pathogen blockage by an intact microbiota), the microbiota mediates a second, novel protective function, i.e. pathogen clearance. Here, the normal microbiota re-grows from a state of depletion and disturbed composition and gradually clears even very high pathogen loads from the gut lumen, a site inaccessible to most "classical" immune effector mechanisms. In conclusion, sIgA and microbiota serve complementary protective functions. The microbiota confers colonization resistance and mediates pathogen clearance in primary infections, while sIgA protects from disease if the host re-encounters the same pathogen. This has implications for curing S. typhimurium diarrhea and for preventing transmission.

Update on mucosal immunoglobulin A in gastrointestinal disease.

PURPOSE OF REVIEW: To review recent findings dealing with the involvement of mucosal immunoglobulin A (IgA) in the gut barrier function and various gastrointestinal diseases. New information will be discussed in the context of previous knowledge in this field. RECENT FINDINGS: The epithelial barrier function seems to be central in many mucosal disorders because it is decisive for host-microbial interactions and penetration of soluble antigens into the lamina propria. Secretory IgA contributes to the barrier function and recent evidence strongly supports the notion that such antibodies are involved in immunological homeostasis. SUMMARY: Inflammatory bowel disease involves a break of tolerance to the commensal microbiota. Aberrations in the mucosal IgA system may, therefore, be part of the inflammatory bowel disease pathogenesis. In gluten-induced enteropathy, however, it has been suggested that a mucosal IgA response may promote the progression of celiac disease and dermatitis herpetiformis by enhancing the uptake of gluten peptides and inhibiting the enzyme activity of tissue transglutaminase. A mucosal IgA response may also promote gastritis by protecting Helicobacter pylori from complement attack. In food allergy, several facets of the epithelial barrier function may show deficiency, including secretory IgA.

Secretory-IgA antibodies play an important role in the immunity to Streptococcus pneumoniae.

This study was designed to investigate whether secretory-IgA (S-IgA) Abs induced by a pneumococcal surface protein A (PspA)-based nasal vaccine are necessary for prevention of streptococcal colonization. Mice nasally immunized with PspA plus a plasmid expressing Flt3 ligand (pFL) cDNA as a mucosal adjuvant showed significantly higher levels of PspA-specific S-IgA and IgG Ab responses in both plasma and nasal washes when compared with naive mice. Although IgA(-/-) mice given nasal PspA plus pFL had significantly high levels of PspA-specific IgG Abs, high numbers of CFUs were detected in nasal washes and nasal passages. In contrast, vaccinated wild-type mice showed essentially no bacteria in the nasal cavity. Further, a nasal vaccine consisting of PspA plus pFL effectively reduced pre-existing Streptococcus pneumoniae in the nasal cavity. These results show that PspA-based vaccine-induced specific S-IgA Abs play a necessary role in the regulation of S. pneumoniae colonization in the nasal cavity.