Epithelial retinoic acid receptor ß regulates serum amyloid A expression and vitamin A-dependent intestinal immunity.

Vitamin A is a dietary component that is essential for the development of intestinal immunity. Vitamin A is absorbed and converted to its bioactive derivatives retinol and retinoic acid by the intestinal epithelium, yet little is known about how epithelial cells regulate vitamin A-dependent intestinal immunity. Here we show that epithelial cell expression of the transcription factor retinoic acid receptor ß (RARß) is essential for vitamin A-dependent intestinal immunity. Epithelial RARß activated vitamin A-dependent expression of serum amyloid A (SAA) proteins by binding directly to Saa promoters. In accordance with the known role of SAAs in regulating Th17 cell effector function, epithelial RARß promoted IL-17 production by intestinal Th17 cells. More broadly, epithelial RARß was required for the development of key vitamin A-dependent adaptive immune responses, including CD4+ T-cell homing to the intestine and the development of IgA-producing intestinal B cells. Our findings provide insight into how the intestinal epithelium senses dietary vitamin A status to regulate adaptive immunity, and highlight the role of epithelial cells in regulating intestinal immunity in response to diet.

Water intake accelerates ATP release from myofibroblast cells in rats: ATP-mediated podoplanin-dependent control for physiological function and immunity.

We previously demonstrated that water intake increased mesenteric lymph flow and the total flux of IL-22 in rat jejunum. The drained water and the higher permeability of albumin in the jejunal microcirculation contributed to increase the lymph flow and IL-22 transport via the activation of great bulk flow in the jejunal villi. To address the effects of water intake-mediated great bulk flow-dependent mechanical force on jejunal physiological function and immunological regulation of innate lymphoid cells (ILC)-3, we examined the effects of shear stress stimulation on cultured rat myofibroblast cells. Next, we investigated the effects of water intake on podoplanin and IL-22 expressions in cultured human intestinal epithelial cells and rat in vivo jejunal preparations, respectively. Shear stress stimulation of the myofibroblast cells induced ATP release via an activation of cell surface F1/F0 ATP synthase. ATP produced podoplanin expression in the intestinal epithelial cells. Water intake accelerated immunohistochemical expressions of podoplanin and IL-22 in the interepithelial layers and lamina propria of the jejunum. ATP dose-dependently increased IL-22 mRNA expression in ILC-3, which are housed in the lamina propria. Water intake also increased immunohistochemical and mRNA expressions of ecto-nucleoside triphosphate diphosphohydrolases 2 and 5 in jejunal villi. In conclusion, water intake-mediated shear stress stimulation-dependent ATP release from myofibroblast cells maintains higher tissue colloid osmotic pressure in the jejunal microcirculation through podoplanin upregulation in the interepithelial layers. ATP induces IL-22 mRNA expression in ILC-3 in jejunal villi, which may contribute to regulation of mucosal immunity in small intestine.NEW & NOTEWORTHY We investigated effects of shear stress stimulation on cultured myofibroblast cells and water intake on podoplanin and IL-22 expressions in rat jejunal villi. The stimulation induced ATP release from the cells. Water intake accelerated podoplanin and IL-22 expression levels. ATP increased IL-22 mRNA expression in innate lymphoid cells (ILC)-3. Hence, water intake maintains higher osmotic pressure in the jejunal villi through ATP release and podoplanin upregulation. Water intake may regulate the mucosal immunity.

Development of the Microbiota and Associations With Birth Mode, Diet, and Atopic Disorders in a Longitudinal Analysis of Stool Samples, Collected From Infancy Through Early Childhood.

BACKGROUND & AIMS: Establishment of the gastrointestinal microbiota during infancy affects immune system development and oral tolerance induction. Perturbations in the microbiome during this period can contribute to development of immune-mediated diseases. We monitored microbiota maturation and associations with subsequent development of allergies in infants and children. METHODS: We collected 1453 stool samples, at 5, 13, 21, and 31 weeks postpartum (infants), and once at school age (6-11 years), from 440 children (49.3% girls, 24.8% born by cesarean delivery; all children except for 6 were breastfed for varying durations; median 40 weeks; interquartile range, 30-53 weeks). Microbiota were analyzed by amplicon sequencing. Children were followed through 3 years of age for development of atopic dermatitis; data on allergic sensitization and asthma were collected when children were school age. RESULTS: Diversity of fecal microbiota, assessed by Shannon index, did not differ significantly among children from 5 through 13 weeks after birth, but thereafter gradually increased to 21 and 31 weeks. Most bacteria within the Bacteroidetes and Proteobacteria phyla were already present at 5 weeks after birth, whereas many bacteria of the Firmicutes phylum were acquired at later times in infancy. At school age, many new Actinobacteria, Firmicutes, and Bacteroidetes bacterial taxa emerged. The largest increase in microbial diversity occurred after 31 weeks. Vaginal, compared with cesarean delivery, was most strongly associated with an enrichment of Bacteroides species at 5 weeks through 31 weeks. From 13 weeks onward, diet became the most important determinant of microbiota composition; cessation of breastfeeding, rather than solid food introduction, was associated with changes. For example, Bifidobacteria, staphylococci, and streptococci significantly decreased on cessation of breastfeeding, whereas bacteria within the Lachnospiraceae family (Pseudobutyrivibrio, Lachnobacterium, Roseburia, and Blautia) increased. When we adjusted for confounding factors, we found fecal microbiota composition to be associated with development of atopic dermatitis, allergic sensitization, and asthma. Members of the Lachnospiraceae family, as well as the genera Faecalibacterium and Dialister, were associated with a reduced risk of atopy. CONCLUSIONS: In a longitudinal study of fecal microbiota of children from 5 weeks through 6 to 11 years, we tracked changes in diversity and composition associated with the development of allergies and asthma.

Role of mucosal immune response and histopathological study in European eel (Anguilla anguilla L.) intraperitoneal challenged by Vibrio anguillarum or Tenacibaculum soleae.

The external mucus layer that covers fish skin contains numerous immune substances scarcely studied that act as the first line of defence against a broad spectrum of pathogens. This study aimed to characterize and describe for the first time several humoral immune defence parameters in the skin mucus of the European eel (Anguilla anguilla) after intraperitoneal injection with Vibrio anguillarum or Tenacibaculum soleae. This study evaluated several immune-related enzymes and bactericidal activity against fish pathogenic bacteria in the skin mucus of European eels at 24, 48, and 72 h post-challenge. The results demonstrated that European eel skin mucus showed significant increments in peroxidase and lysozyme activity at 48 and 72 h after V. anguillarum challenge, compared to other experimental groups. In the case of antiprotease activity, an increase was observed at 24 h in the skin mucus of fish challenged with V. anguillarum compared to unchallenged fish, while this activity was undetected at 48 and 72 h. In contrast, protease activity had decreased at 48 and 72 h in the skin mucus of fish challenged with V. anguillarum compared to the unchallenged group. Regarding bactericidal activity, a high growth capacity of T. soleae was observed in the skin mucus of all experimental groups. Interestingly, the skin mucus from fish challenged with V. anguillarum exhibited increased bactericidal activity against this bacterium at 48 h, compared to unchallenged fish. Finally, severe histopathological alterations were observed in the gills and liver at the end of the trial (72 h), whereas the skin showed only an overspread presence of goblet cells in the challenged fish compared to unchallenged fish. The present results may give new insights into the mucosal immune system of this primitive species with potential applications in aquaculture.

The role of nasal congestion as a defence against respiratory viruses.

INTRODUCTION: This review discusses how nasal congestion may have benefits as a mechanism of defence against respiratory viruses. METHODS: A literature research was conducted on respiratory viruses and nasal congestion, following a recently published review on how temperature sensitivity is important for the success of common respiratory viruses. RESULTS: The literature reported that common respiratory viruses are temperature sensitive and replicate well at the cooler temperatures of the upper airways (32°C), but replication is restricted at body temperature (37°C). The amplitude of the phases of congestion and decongestion associated with the nasal cycle was increased on infection with respiratory viruses and this caused unilateral nasal congestion and obstruction. Nasal congestion and obstruction increase nasal mucosal temperature towards 37°C and therefore restricted the replication of respiratory viruses. CONCLUSION: Nasal congestion associated with the nasal cycle may act as a mechanism of respiratory defence against infection with respiratory viruses.

Intranasal delivery of a nicotine vaccine candidate induces antibodies in mouse blood and lung mucosal secretions that specifically neutralize nicotine.

OBJECTIVE: Cigarette smoking is one of the leading causes of death in the world. The majority of the smokers have tried to quit, but only a few of them were able to achieve long-term abstinence, due to the high addictiveness of nicotine. Nicotine-specific antibodies have the potential to block the euphoric effect of nicotine by forming antibody-antigen complexes in the blood circulation. Since nicotine is taken largely by inhalation, inducing anti-nicotine antibodies in lung and nasal mucosal secretions, in addition to blood circulation, is expected to be beneficial. SIGNIFICANCE: The importance of this study is to establish the feasibility of inducing nicotine-neutralizing antibodies not only in the blood, but also in the lung and nasal mucosal secretions, by intranasal administration of a nicotine vaccine candidate. METHODS: Nicotine-keyhole limpet hemocyanin conjugate (Nic-KLH) was prepared and mixed with monophosphoryl lipid A (MPL) as an adjuvant. Nic-KLH/MPL was given intranasally or subcutaneously to mice, and the titers, affinity, and specificity of the nicotine-specific antibodies in nasal and lung mucosal secretions and blood samples were determined using (competitive) ELISA. RESULTS: Nasal Nic-KLH/MPL immunization elicited robust nicotine-specific neutralizing IgA in mouse nasal and lung secretions, in additional to anti-nicotine IgG in blood circulation. The nicotine-specific IgG level in mice nasally immunized with Nic-KLH/MPL was lower than in mice subcutaneously immunized with the same Nic-KLH/MPL, but a heterologous prime-boost immunization strategy helped to increase it. CONCLUSION: Intranasal immunization with a nicotine vaccine candidate can induce systemic and mucosal antibodies that specifically neutralize nicotine.

The proliferation and clonal migration of B cells in the systemic and mucosal tissues of channel catfish suggests there is an interconnected mucosal immune system.

IgM transcripts from different mucosal and systemic tissues from a single adult channel catfish have been evaluated. Arrayed heavy chain cDNA libraries from each of these different mucosal and systemic tissues were separately constructed, hybridized with VH family specific probes and a variety of approaches were used to define their structural relationships. Baseline hybridization studies indicated that the tissue libraries had different VH expression patterns, and sequencing studies indicated this was not simply due to varying proportions of the same B cell population. In the systemic tissues of PBL, spleen, and anterior kidney >95% of the sequenced clones in the arrayed libraries represented different heavy chain rearrangements. Diversity was also found in the mucosal libraries of skin, gill lamellae, and two non-adjoining regions of the intestine, but additional populations were identified which indicated localized clonal expansion. Various clonal sets were characterized in detail, and their genealogies indicated somatic mutation accompanied localized clonal expansion with some members undergoing additional mutations and expansion after migration to different mucosal sites. PCR analyses indicated these mucosal clonal sets were more abundant within different mucosal tissues rather than in the systemic tissues. These studies indicate that the mucosal immune system in fish can express B cell transcripts differently from those found systemically. These studies further indicate that the mucosal immune system is interconnected with clonal B cells migrating between different mucosal tissues, results which yield new insight into immune diversity in early vertebrate phylogeny.

Atlantic salmon (Salmo salar) mounts systemic and mucosal stress responses to peracetic acid.

Peracetic acid (PAA), a strong organic peroxide, is considered a relatively sustainable disinfectant in aquaculture because of its broad effectivity against many pathogens at low concentrations and because it degrades spontaneously to harmless residues. The impacts of PAA on fish health must be determined before its use as either a routine disinfectant or chemotherapeutant. Here we investigated the systemic and mucosal stress responses of Atlantic salmon (Salmo salar) to PAA. In experiment 1, salmon were exposed to different nominal concentrations (0, 0.6, and 2.4 ppm) of PAA for 5 min, followed by a re-exposure to the same concentrations for 30 min 2 weeks later. Sampling was performed before exposure to PAA and at 2 h, 48 h, and 2 w after exposures. In experiment 2, fish were subjected to crowding stress prior to PAA exposure at 4.8 ppm for 30 min. The fish were sampled before exposure and 1 h, 4 h, and 2 w after. The two trials were performed in a recirculation system. Both systemic (i.e., plasma cortisol, glucose, lactate, total antioxidant capacity) and mucosal (i.e., expression of antioxidant coding genes in the skin and gills) stress indicators were affected by the treatments at varying levels, and it was apparent that the fish were able to mount a robust response to the physiological demands of PAA exposure. The cortisol levels increased in the early hours after exposure and returned to basal level afterwards. Prior exposure history to PAA did not markedly affect the levels of plasma lactate and glucose when fish were re-exposed to PAA. Crowding stress before PAA treatment, however, did alter some of the stress indicators (i.e., lactate, glucose and expression of antioxidant genes in the gills), suggesting that stress history serves as both a confounding and compounding factor on how stress responses to PAA are mobilised. Nonetheless, the changes were not substantial. Gene expression profile analyses revealed that the antioxidant system was more responsive to PAA in the gills than in the skin. The increased antioxidant capacity in the plasma, particularly at 2.4 ppm and higher, indicates that antioxidants were produced to neutralise the internal redox imbalance resulting from PAA exposure. In conclusion, the results show that salmon were able to mount a robust adaptive response to different PAA doses and exposure times, and a combined exposure to stress and PAA. These results underscore the potential of PAA as a chemotherapeutant for salmon at PAA concentrations commonly applied to control parasitic infestations.

Gut symbiotic microbes imprint intestinal immune cells with the innate receptor SLAMF4 which contributes to gut immune protection against enteric pathogens.

BACKGROUND: Interactions between host immune cells and gut microbiota are crucial for the integrity and function of the intestine. How these interactions regulate immune cell responses in the intestine remains a major gap in the field. AIM: We have identified the signalling lymphocyte activation molecule family member 4 (SLAMF4) as an immunomodulator of the intestinal immunity. The aim is to determine how SLAMF4 is acquired in the gut and what its contribution to intestinal immunity is. METHODS: Expression of SLAMF4 was assessed in mice and humans. The mechanism of induction was studied using GFPtg bone marrow chimaera mice, lymphotoxin α and TNLG8A-deficient mice, as well as gnotobiotic mice. Role in immune protection was revealed using oral infection with Listeria monocytogenes and Cytobacter rodentium. RESULTS: SLAMF4 is a selective marker of intestinal immune cells of mice and humans. SLAMF4 induction occurs directly in the intestinal mucosa without the involvement of the gut-associated lymphoid tissue. Gut bacterial products, particularly those of gut anaerobes, and gut-resident antigen-presenting cell (APC) TNLG8A are key contributors of SLAMF4 induction in the intestine. Importantly, lack of SLAMF4 expression leads the increased susceptibility of mice to infection by oral pathogens culminating in their premature death. CONCLUSIONS: SLAMF4 is a marker of intestinal immune cells which contributes to the protection against enteric pathogens and whose expression is dependent on the presence of the gut microbiota. This discovery provides a possible mechanism for answering the long-standing question of how the intertwining of the host and gut microbial biology regulates immune cell responses in the gut.

Role of the intestinal mucosa in acute gastrointestinal GVHD.

Intestinal graft-versus-host disease (GVHD) remains a significant obstacle to the success of allogeneic hematopoietic cell transplantation. The intestinal mucosa comprises the inner lining of the intestinal tract and maintains close proximity with commensal microbes that reside within the intestinal lumen. Recent advances have significantly improved our understanding of the interactions between the intestinal mucosa and the enteric microbiota. Changes in host mucosal tissue and commensals posttransplant have been actively investigated, and provocative insights into mucosal immunity and the enteric microbiota are now being translated into clinical trials of novel approaches for preventing and treating acute GVHD. In this review, we summarize recent findings related to aspects of the intestinal mucosa during acute GVHD.

Linking stress and immunity: Immunoglobulin A as a non-invasive physiological biomarker in animal welfare studies.

As the animal welfare community strives to empirically assess how care and management practices can help maintain or even enhance welfare, the development of tools for non-invasively measuring physiological biomarkers is essential. Of the suite of physiological biomarkers, Immunoglobulin A (IgA), particularly the secretory form (Secretory IgA or SIgA), is at the forefront because of its crucial role in mucosal immunity and links to physical health, stress, and overall psychological well-being. While interpretation of changes in SIgA concentrations on short time scales is complex, long-term SIgA patterns are consistent: conditions that create chronic stress lead to suppression of SIgA. In contrast, when welfare is enhanced, SIgA is predicted to stabilize at higher concentrations. In this review, we examine how SIgA concentrations are reflective of both physiological stress and immune function. We then review the literature associating SIgA concentrations with various metrics of animal welfare and provide detailed methodological considerations for SIgA monitoring. Overall, our aim is to provide an in-depth discussion regarding the value of SIgA as physiological biomarker to studies aiming to understand the links between stress and immunity.

Ribosome Inactivation Leads to Attenuation of Intestinal Polymeric Ig Receptor Expression via Differential Regulation of Human Antigen R.

The polymeric IgR (pIgR) is a central component in the transport of IgA across enterocytes and thereby plays a crucial role in the defense against enteropathogens and in the regulation of circulating IgA levels. The present study was performed to address the novel regulation of pIgR expression in intestinal epithelia undergoing ribosome inactivation. Insults to mucosa that led to ribosome inactivation attenuated pIgR expression in enterocytes. However, IFN regulatory factor-1 (IRF-1) as a central transcription factor of pIgR induction was superinduced by ribosome inactivation in the presence of IFN-γ as a result of mRNA stabilization by the RNA-binding protein HuR. Another important transcription factor for pIgR expression, NF-κB, was marginally involved in suppression of pIgR by ribosome inactivation. In contrast to a positive contribution of HuR in early induction of IRF-1 expression, extended exposure to ribosome inactivation caused nuclear entrapment of HuR, resulting in destabilization of late-phase-induced pIgR mRNA. These HuR-linked differential regulations of pIgR and of IRF-1 led to a reduced mucosal secretion of IgA and, paradoxically, an induction of IRF-1-activated target genes, including colitis-associated IL-7. Therefore, these events can account for ribosome inactivation-related mucosal disorders and provide new insight into interventions for HuR-linked pathogenesis in diverse mucosa-associated diseases, including inflammatory bowel disease and IgA nephritis.

IL-33 promotes an innate immune pathway of intestinal tissue protection dependent on amphiregulin-EGFR interactions.

The barrier surfaces of the skin, lung, and intestine are constantly exposed to environmental stimuli that can result in inflammation and tissue damage. Interleukin (IL)-33-dependent group 2 innate lymphoid cells (ILC2s) are enriched at barrier surfaces and have been implicated in promoting inflammation; however, the mechanisms underlying the tissue-protective roles of IL-33 or ILC2s at surfaces such as the intestine remain poorly defined. Here we demonstrate that, following activation with IL-33, expression of the growth factor amphiregulin (AREG) is a dominant functional signature of gut-associated ILC2s. In the context of a murine model of intestinal damage and inflammation, the frequency and number of AREG-expressing ILC2s increases following intestinal injury and genetic disruption of the endogenous AREG-epidermal growth factor receptor (EGFR) pathway exacerbated disease. Administration of exogenous AREG limited intestinal inflammation and decreased disease severity in both lymphocyte-sufficient and lymphocyte-deficient mice, revealing a previously unrecognized innate immune mechanism of intestinal tissue protection. Furthermore, treatment with IL-33 or transfer of ILC2s ameliorated intestinal disease severity in an AREG-dependent manner. Collectively, these data reveal a critical feedback loop in which cytokine cues from damaged epithelia activate innate immune cells to express growth factors essential for ILC-dependent restoration of epithelial barrier function and maintenance of tissue homeostasis.

Intestinal dendritic cells in the regulation of mucosal immunity.

The intestine presents a huge surface area to the outside environment, a property that is of critical importance for its key functions in nutrient digestion, absorption, and waste disposal. As such, the intestine is constantly exposed to dietary and microbial-derived foreign antigens, to which immune cells within the mucosa must suitably respond to maintain intestinal integrity, while also providing the ability to mount effective immune responses to potential pathogens. Dendritic cells (DCs) are sentinel immune cells that play a central role in the initiation and differentiation of adaptive immune responses. In the intestinal mucosa, DCs are located diffusely throughout the intestinal lamina propria, within gut-associated lymphoid tissues, including Peyer's patches and smaller lymphoid aggregates, as well as in intestinal-draining lymph nodes, including mesenteric lymph nodes. The recognition that dietary nutrients and microbial communities in the intestine influence both mucosal and systemic immune cell development and function as well as immune-mediated disease has led to an explosion of literature in mucosal immunology in recent years and a growing interest in the functionality of intestinal DCs. In the current review, we discuss recent findings from our group and others that have provided important insights regarding murine and human intestinal lamina propria DCs and highlighted marked developmental and functional heterogeneity within this compartment. A thorough understanding of the role these subsets play in the regulation of intestinal immune homeostasis and inflammation will help to define novel strategies for the treatment of intestinal pathologies and contribute to improved rational design of mucosal vaccines.

Yoga stretching for improving salivary immune function and mental stress in middle-aged and older adults.

Protection against age-related immune suppression is important in elderly individuals. This study determined the effect of yoga on mucosal immune function and mental stress. Saliva samples were collected from 23 adult women (age: 60.4 ± 10.4 years) before and after 90 minutes of yoga stretching or rest to measure secretory immunoglobulin A (SIgA), cortisol, and testosterone. The SIgA concentration and secretion rate were significantly higher after yoga than before (p < .05). The cortisol concentration and secretion rate were lower and testosterone secretion rate higher after yoga (p < .05). Yoga stretching can reduce stress and enhance mucosal immune function in elderly women.

Gastrointestinal immune and microbiome changes during parenteral nutrition.

Parenteral nutrition (PN) is a lifesaving therapy that provides intravenous nutrition support to patients who cannot, or should not, feed via the gastrointestinal (GI) tract. Unfortunately, PN also carries certain risks related to infection and metabolic complications compared with enteral nutrition. In this review, an overview of PN and GI immune and microbiome changes is provided. PN impacts the gut-associated lymphoid tissue functions, especially adaptive immune cells, changes the intestinal epithelium and chemical secretions, and significantly alters the intestinal microbiome. Collectively, these changes functionally result in increased susceptibility to infectious and injurious challenge. Since PN remains necessary in large numbers of patients, the search to improve outcomes by stimulating GI immune function during PN remains of interest. This review closes by describing recent advances in using enteric nervous system neuropeptides or microbially derived products during PN, which may improve GI parameters by maintaining immunity and physiology.

Understanding the gut microbiome of dairy calves: Opportunities to improve early-life gut health.

Early gut microbiota plays a vital role in the long-term health of the host. However, understanding of these microbiota is very limited in livestock species, especially in dairy calves. Neonatal calves are highly susceptible to enteric infections, one of the major causes of calf death, so approaches to improving gut health and overall calf health are needed. An increasing number of studies are exploring the microbial composition of the gut, the mucosal immune system, and early dietary interventions to improve the health of dairy calves, revealing possibilities for effectively reducing the susceptibility of calves to enteric infections while promoting growth. Still, comprehensive understanding of the effect of dietary interventions on gut microbiota-one of the key aspects of gut health-is lacking. Such knowledge may provide in-depth understanding of the mechanisms behind functional changes in response to dietary interventions. Understanding of host-microbial interactions with dietary interventions and the role of the gut microbiota during pathogenesis at the site of infection in early life is vital for designing effective tools and techniques to improve calf gut health.

Lactobacillus helveticus Lafti L10 Supplementation Modulates Mucosal and Humoral Immunity in Elite Athletes: A Randomized, Double-Blind, Placebo-Controlled Trial.

Michalickova, DM, Kostic-Vucicevic, MM, Vukasinovic-Vesic, MD, Stojmenovic, TB, Dikic, NV, Andjelkovic, MS, Djordjevic, BI, Tanaskovic, BP, and Minic, RD. Lactobacillus helveticus Lafti L10 supplementation modulates mucosal and humoral immunity in elite athletes: a randomized, double-blind, placebo-controlled trial. J Strength Cond Res 31(1): 62-70, 2017-To test the influence of probiotic supplementation on humoral immune response, a double-blind, placebo-controlled trial was conducted. Thirty athletes (24 males and 6 females, females: V[Combining Dot Above]O2max 38.2 ± 4.9 ml·kg·min, age 23.2 ± 1.4 years; males: V[Combining Dot Above]O2max 57.5 ± 9.2 ml·kg·min, age 24.0 ± 2.4 years, mean ± SD) were randomized either to the probiotic group (Lactobacillus helveticus Lafti L10, 2 × 10 colony-forming units) or to the placebo group. Serum and saliva samples were collected at the baseline and after 14 weeks. Total and specific antibacterial antibody levels of IgM, IgG, and IgA classes were determined for different bacteria in the serum, and in saliva, total and specific antibacterial IgA levels were examined. Total IgM was elevated in both probiotic (18%, 15-20%; mean, 90% confidence interval; p = 0.02) and placebo group (35%, 22-47%; p = 0.02), without observed differences in changes between the groups. No significant changes in IgM levels specific for tested bacteria were found. Total IgG level was constant in both groups. A significant (16%, -2.8 to 35%, p = 0.04) reduction of anti-Enterococcus faecalis IgG was noted in the placebo group, in comparison with the probiotic group. There was a substantial decrease in total IgA level in the placebo group, when measured either in serum (15%, 12-18%, p = 0.04) or in saliva (35%, -1.4 to 53%, p = 0.03). Significantly reduced levels of serum anti-lactic acid bacteria IgA antibodies in the placebo group compared with the probiotic group were detected for Lactobacillus rhamnosus LA68 (24%, 5.8-42%, p = 0.02) and for L. rhamnosus LB64 (15%, 2.7-27%, p = 0.02). Probiotic administration could have beneficial effects on systemic humoral and mucosal immune responses.

Loss of Innate Host Defense Following Unprotected Vaginal Sex.

BACKGROUND: Multiple host defense mechanisms protect the female genital tract from pathogens, but the impact of sexual intercourse on defense is unknown. METHODS: As part of a hypothesis-generating study, 17 women provided cervicovaginal lavage (CVL) specimens at baseline (all had abstained from sexual intercourse, masturbation, and vaginal product use for 72 hours prior to screening), 2-6 hours and 10-14 hours after vaginal intercourse with a male condom, and 2-6 hours and 10-14 hours after vaginal intercourse without a male condom (5 visits total, including the baseline visit). Vaginal pH, concentrations of immune molecules, and antimicrobial activity at postcoital visits were compared to baseline values. RESULTS: Vaginal pH and the transforming growth factor ß1 level increased, but human beta-defensin 2 (HBD-2), HBD-3, and interleukin 8 levels decreased after unprotected sex. Median Escherichia coli inhibitory activity in CVL specimens decreased significantly from baseline at the visit 2-6 hours after unprotected sex (63% [range, -34% to 99%] vs 5% [range, -51% to 100%]; P = .02) and remained low at the visit 10-14 hours after unprotected sex (6% [range, -19% to 92%]; P = .02). Pooled human seminal plasma enhanced E. coli growth in vitro in a dose-dependent manner and, when added to CVL samples with high anti-E. coli activity, reversed the inhibition. CONCLUSIONS: Unprotected vaginal sex results in a reduction in endogenous anti-E. coli activity, which may reflect, in part, enhancement of bacterial growth by seminal plasma. This finding may contribute to the risk of E. coli vaginal colonization following sexual intercourse.