Targeting the Cutaneous Microbiota in Atopic Dermatitis by Coal Tar via AHR-Dependent Induction of Antimicrobial Peptides.

Skin colonization by Staphylococcus aureus and its relative abundance is associated with atopic dermatitis (AD) disease severity and treatment response. Low levels of antimicrobial peptides in AD skin may be related to the microbial dysbiosis. Therapeutic targeting of the skin microbiome and antimicrobial peptide expression can, therefore, restore skin homeostasis and combat AD. In this study, we analyzed the cutaneous microbiome composition in 7 patients with AD and 10 healthy volunteers upon topical coal tar or vehicle treatment. We implemented and validated a Staphylococcus-specific single-locus sequence typing approach combined with classic 16S ribosomal RNA marker gene sequencing to study the bacterial composition. During coal tar treatment, Staphylococcus abundance decreased, and Propionibacterium abundance increased, suggesting a shift of the microbiota composition toward that of healthy controls. We, furthermore, identified a hitherto unknown therapeutic mode of action of coal tar, namely the induction of keratinocyte-derived antimicrobial peptides via activation of the aryl hydrocarbon receptor. Restoring antimicrobial peptide levels in AD skin via aryl hydrocarbon receptor-dependent transcription regulation can be beneficial by creating a (anti)microbial milieu that is less prone to infection and inflammation. This underscores the importance of coal tar in the therapeutic aryl hydrocarbon receptor armamentarium and highlights the aryl hydrocarbon receptor as a target for drug development.

Psoriatic lesions are characterized by higher bacterial load and imbalance between Cutibacterium and Corynebacterium.

BACKGROUND: Several studies have found that the microbiota of psoriatic lesions is different from that of healthy skin. OBJECTIVE: To characterize the microbiota of lesional and unaffected skin in patients with psoriasis and controls and investigate the correlation between cutaneous microbiota and clinical features of psoriasis. METHODS: Using quantitative polymerase chain reaction and 16S rRNA sequencing, we assayed the profiles of cutaneous microbiota in controls, unaffected skin, and psoriatic lesions. We also investigated the correlation of psoriasis-associated taxa with clinical characteristics. RESULTS: High bacterial load was identified in the psoriatic lesions compared with unaffected skin and controls. There was an imbalance between Cutibacterium (also known as Propionibacterium) and Corynebacterium in psoriatic skin. Lesions showed a higher proportion of Corynebacterium and a lower proportion of Cutibacterium compared with unaffected skin and controls. Corynebacterium was correlated with the severity of local lesions, whereas Cutibacterium showed correlation with the abnormity of skin capacitance. LIMITATIONS: We did not conduct a longitudinal study. CONCLUSIONS: Psoriatic lesions are characterized by higher bacterial load and imbalance between Cutibacterium and Corynebacterium.

Regulation of Th17 cells by P. UF1 against systemic Listeria monocytogenes infection.

Regulation of Th17 and Th1 cell responses against intracellular pathogens, including Listeria monocytogenes (L. m), is critical to limit inflammation-induced tissue damage. We recently demonstrated the ability of P. UF1 bacterium derived from the intestinal bacterial commensals of preterm infants fed human breast milk to significantly mitigate pathogen-induced inflammation limiting colonic tissue damage. Here we further elucidated the potential of P. UF1 to also regulate innate and T cells, particularly Th17 and Th1 cells, against systemic L. m infection. Data demonstrate that P. UF1 not only robustly regulated protective Th17 and Th1 cells, but also sustained regulatory T cells (Treg cells) resulting in accelerated L. m clearance. Together, regulation of pathogenic inflammation by a novel probiotic bacterium such as P. UF1 may illuminate a new strategy to specifically control Th17-Th1 cells via IL-10+ Treg cells to limit systemic tissue damage induced by intracellular pathogens, including L. m.

Commensal Propionibacterium strain UF1 mitigates intestinal inflammation via Th17 cell regulation.

Consumption of human breast milk (HBM) attenuates the incidence of necrotizing enterocolitis (NEC), which remains a leading and intractable cause of mortality in preterm infants. Here, we report that this diminution correlates with alterations in the gut microbiota, particularly enrichment of Propionibacterium species. Transfaunation of microbiota from HBM-fed preterm infants or a newly identified and cultured Propionibacterium strain, P. UF1, to germfree mice conferred protection against pathogen infection and correlated with profound increases in intestinal Th17 cells. The induction of Th17 cells was dependent on bacterial dihydrolipoamide acetyltransferase (DlaT), a major protein expressed on the P. UF1 surface layer (S-layer). Binding of P. UF1 to its cognate receptor, SIGNR1, on dendritic cells resulted in the regulation of intestinal phagocytes. Importantly, transfer of P. UF1 profoundly mitigated induced NEC-like injury in neonatal mice. Together, these results mechanistically elucidate the protective effects of HBM and P. UF1-induced immunoregulation, which safeguard against proinflammatory diseases, including NEC.

Immunomodulation properties of multi-species fermented milks.

Dairy propionibacteria (PAB) are used as a ripening starter in combination with Lactic acid bacteria (LAB) for dairy products such as Swiss-type cheese. LAB and PAB have also been studied for their probiotic properties but little is still known about their individual and/or synergistic beneficial effects within dairy matrices. In the context of a rising incidence of Inflammatory Bowel Diseases, it has become crucial to evaluate the immunomodulatory potential of bacteria ingested in large numbers via dairy products. We therefore selected different strains and combinations of technological LAB and PAB. We determined their immunomodulatory potential by IL-10 and IL-12 induction, in human peripheral blood mononuclear cells, on either single or mixed cultures, grown on laboratory medium or directly in milk. Milk was fermented with selected anti-inflammatory strains of LAB or PAB/LAB mixed cultures and the resulting bacterial fractions were also evaluated for these properties, together with starter viability and optimum technological aspects. The most promising fermented milks were evaluated in the context of TNBS- or DSS-induced colitis in mice. The improvement in inflammatory parameters evidenced an alleviation of colitis symptoms as a result of fermented milk consumption. This effect was clearly strain-dependent and modulated by growth within a fermented dairy product. These findings offer new tools and perspectives for the development of immunomodulatory fermented dairy products for targeted populations.

Propionibacterium species and follicular keratinocyte activation in acneic and normal skin.

BACKGROUND: The pathogenesis of acne vulgaris is multifactorial with increased sebum production, alteration in the quality of sebum lipids, dysregulation of the hormone microenvironment, follicular hyperkeratinization and Propionibacterium acnes-driven inflammation as major contributory factors. Hyperproliferation of keratinocytes is believed to contribute to hypercornification and eventually leads to comedone development. While the distribution of P. acnes is relatively well documented in acneic and healthy skin, little is known about P. granulosum and P. avidum. OBJECTIVES: To visualize directly the three major Propionibacterium in 117 control and 26 acneic skin samples. In addition, keratinocyte proliferation was evaluated. METHODS: Propionibacteria were visualized by immunofluorescence microscopy, and keratinocyte proliferation was assessed by Ki67, keratin (K) 16 and p63 immunochemistry. RESULTS: P. acnes was identified in 68 samples (48%), while P. granulosum was identified in 12 (8%) samples; P. avidum was not detected at all. Unexpectedly, acne samples did not show higher keratinocyte proliferation than controls, nor was there any association between bacterial colonization and expression of Ki67/K16/p63. CONCLUSIONS: Our findings do not support earlier notions of follicular keratinocyte hyperproliferation as a cause of ductal hypercornification in acneic facial skin. Further studies on the mechanisms underlying hypercornification in acne pathogenesis are needed.

Etiologic role of infectious agents.

A consensus statement found in most peer-reviewed literature on sarcoidosis is that the etiology of sarcoidosis is unknown. It is timely to review whether this statement should be revised. Many infectious agents meet the basic requirements of inducing granulomatous inflammation and immunologic responses consistent with sarcoidosis including oligoclonal expansion of CD4+ T cells, polarized Th1 and possibly Th17 responses, and dysregulated regulatory T-cell function. Studies over the past decade provide increasing and complementary data to implicate a role for infectious agents in sarcoidosis etiology. These studies used different methodologies such as polymerase chain reaction and mass spectrometry to document microbial nucleic acids and proteins in sarcoidosis tissues. Multiple studies report antigen-specific immune responses to specific microbial proteins in sarcoidosis. In aggregate, these studies provide compelling evidence that mycobacteria play a major etiologic role in sarcoidosis in the United States and Europe. Studies from Japan support a role for Propionibacteria as a major etiologic agent in the country. There is controversy over how these (or other) infectious agents cause sarcoidosis. The hypothesis that chronic sarcoidosis is caused by a viable, replicating mycobacterial or other infection has no direct pathologic, microbiologic, or clinical evidence. A novel hypothesis links microbial triggers to a sarcoidosis outcome from the accumulation of aggregated proinflammatory serum amyloid A within granulomas, providing a mechanism for chronic disease in the absence of any viable tissue infection. Further studies are needed to provide more definitive evidence for these competing hypotheses before the statement that the etiology of sarcoidosis is unknown becomes obsolete.

Contribution of surface ß-glucan polysaccharide to physicochemical and immunomodulatory properties of Propionibacterium freudenreichii.

Propionibacterium freudenreichii is a bacterial species found in Swiss-type cheeses and is also considered for its health properties. The main claimed effect is the bifidogenic property. Some strains were shown recently to display other interesting probiotic potentialities such as anti-inflammatory properties. About 30% of strains were shown to produce a surface exopolysaccharide (EPS) composed of (1→3,1→2)-ß-D-glucan due to a single gene named gtfF. We hypothesized that functional properties of P. freudenreichii strains, including their anti-inflammatory properties, could be linked to the presence of ß-glucan. To evaluate this hypothesis, gtfF genes of three ß-glucan-producing strains were disrupted. These knockout (KO) mutants were complemented with a plasmid harboring gtfF (KO-C mutants). The absence of ß-glucan in KO mutants was verified by immunological detection and transmission electron microscopy. We observed by atomic force microscopy that the absence of ß-glucan in the KO mutant dramatically changed the cell's topography. The capacity to adhere to polystyrene surface was increased for the KO mutants compared to wild-type (WT) strains. Anti-inflammatory properties of WT strains and mutants were analyzed by stimulation of human peripheral blood mononuclear cells (PBMCs). A significant increase of the anti-inflammatory interleukin-10 cytokine production by PBMCs was measured in the KO mutants compared to WT strains. For one strain, the role of ß-glucan in mice gut persistence was assessed, and no significant difference was observed between the WT strain and its KO mutant. Thus, ß-glucan appears to partly hide the anti-inflammatory properties of P. freudenreichii; which is an important result for the selection of probiotic strains.

Promising immunomodulatory effects of selected strains of dairy propionibacteria as evidenced in vitro and in vivo.

Immunomodulatory properties of 10 dairy propionibacteria, analyzed on human peripheral blood mononuclear cells (PBMCs), revealed a highly strain-dependent induction of anti-inflammatory cytokine interleukin 10 (IL-10). Two selected strains of Propionibacterium freudenreichii showed a protective effect against two models of colitis in mice, suggesting a probiotic potential predicted by immune-based selection criteria for these cheese starter bacteria.

The etiologic role of infectious antigens in sarcoidosis pathogenesis.

Sarcoidosis is a disease of unknown etiology, characterized pathologically by noncaseating granulomas that most commonly involve the lung, skin, lymph nodes, and eyes. Syndromes with similar pathological and immunologic features to sarcoidosis such as chronic beryllium disease, hypersensitivity pneumonitis, and tuberculosis illustrate that granulomatous diseases may or may not have an infectious etiology. Although the etiology of sarcoidosis remains unknown, recent molecular, genetic, and immunologic studies strengthen the association of sarcoidosis with infectious antigens. Currently, the strongest agents considered include PROPIONIBACTERIUM and MYCOBACTERIUM species. Independent studies report the presence of microbial nucleic acids and proteins within sarcoidosis specimens. Th-1 immune responses to mycobacterial proteins have been detected within sarcoidosis diagnostic bronchoalveolar lavage (BAL). These proteins are actively secreted by the mycobacterial SecA 2 secretion system and are important to evade the host immune system. Recent discoveries regarding MHC class II alleles provide additional insight regarding the role of microbial antigens in sarcoidosis pathogenesis. Although further investigation is warranted, the recent progress of independent laboratories, using complementary techniques, strengthens the role of microbial antigens in sarcoidosis pathogenesis. These studies lay a strong foundation toward identifying therapeutic targets.

Effect of immunostimulation by detoxified E. coli lipopolysaccharide combined with inactivated Propionibacterium granulosum cells on porcine immunity.

The aim of this experiment was to evaluate the immunomodulating activities of inactivated Propionibacterium granulosum cell walls and E. coli lipopolysaccharide (PG/LPS) on porcine immunity. Piglets were intramuscularly administered PG/LPS (1 ml/10 kg body weight) once or twice. The function of natural killer cells, lymphocytes and neutrophils and the adjuvant effect on antibody induction by attenuated classical swine fever virus (CSFV) and inactivated Mycoplasma hyopneumoniae vaccination were evaluated. The results showed that the cytotoxicity of natural killer cells and proliferation of lymphocytes in response to mitogen stimulation were significantly enhanced (P<0.05) in those pigs receiving PG/LPS injection compared with the controls. However, there was no significant effect on the phagocytic activity of neutrophils (P>0.05). PG/LPS also displayed adjuvant effects with CSFV and Mycoplasma hyopneumoniae vaccines. Moreover, pigs receiving two injections of PG/LPS showed a 20.8% growth enhancement compared with untreated pigs. Thus, PG/LPS caused positive immunoregulation of porcine innate immune system effectors, non-specific activation of lymphocytes and antibody production.

Probiotics prevent IgE-associated allergy until age 5 years in cesarean-delivered children but not in the total cohort.

BACKGROUND: Less microbial exposure in early childhood is associated with more allergic disease later. Allergic children have a different fecal microflora, with less lactobacilli and bifidobacteria. Beneficial effects regarding the development of allergy have been suggested to come through probiotic supplementation. OBJECTIVE: We sought to study the effect of probiotic and prebiotic supplementation in preventing allergies. METHODS: In a double-blinded, placebo-controlled study we randomized 1223 mothers with infants at high risk for allergy to receive a probiotic mixture (2 lactobacilli, bifidobacteria, and propionibacteria) or placebo during the last month of pregnancy and their infants to receive it from birth until age 6 months. Infants also received a prebiotic galacto-oligosaccharide or placebo. At 5 years, we evaluated the cumulative incidence of allergic diseases (eczema, food allergy, allergic rhinitis, and asthma) and IgE sensitization. RESULTS: Of the 1018 intent-to-treat infants, 891 (88%) attended the 5-year visit. Frequencies of allergic and IgE-associated allergic disease and sensitization in the probiotic and placebo groups were similar: 52.6% versus 54.9% and 29.5% versus 26.6%, respectively, and 41.3% in both. No significant difference appeared in frequencies of eczema (39.3% vs 43.3%), atopic eczema (24.0% vs 25.1%), allergic rhinitis (20.7% vs 19.1%), or asthma (13.0% vs 14.1%) between groups. However, less IgE-associated allergic disease occurred in cesarean-delivered children receiving probiotics (24.3% vs 40.5%; odds ratio, 0.47; 95% CI, 0.23% to 0.96%; P = .035). CONCLUSIONS: No allergy-preventive effect that extended to age 5 years was achieved with perinatal supplementation of probiotic bacteria to high-risk mothers and children. It conferred protection only to cesarean-delivered children.

Toll-like receptor 2 mediates inflammatory cytokine induction but not sensitization for liver injury by Propioni- bacterium acnes.

Recognition of Gram-positive bacteria by Toll-like receptor 2 (TLR2) induces activation of proinflammatory pathways. In mice, sensitization with the Gram-positive Propionibacterium acnes followed by a challenge with the TLR4 ligand, lipopolysaccharide (LPS), results in fulminant hepatic failure. Here, we investigated the role of TLR2 in liver sensitization to LPS-induced injury. Stimulation of Chinese hamster ovary cells and peritoneal macrophages with heat-killed P. acnes required expression of TLR2 but not of TLR4, suggesting that P. acnes was a TLR2 ligand. Cell activation by P. acnes was myeloid differentiation primary-response protein 88 (MyD88)-dependent, and it was augmented by coexpression of CD14 in mouse peritoneal macrophages. In vitro, P. acnes behaved as a TLR2 ligand and induced TLR4 hetero- and TLR2 homotolerance in peritoneal macrophages. In vivo priming of wild-type mice with P. acnes, but not with the selective TLR2 ligands peptidoglycan and lipotheicoic acid, resulted in hepatocyte necrosis, hyperelevated serum levels of tumor necrosis factor alpha (TNF-alpha), interleukin (IL)-6, interferon-gamma (IFN-gamma), and IL-12 (p40/p70), and increased RNA expression of proinflammatory cytokines (IL-12p40, IL-1alpha, IL-6, IL-1beta, IL-18, IFN-gamma) in the liver after a LPS challenge. Furthermore, P. acnes priming sensitized TLR2-deficient (TLR2-/-) but not MyD88-/- mice to LPS-induced injury, evidenced by hepatocyte necrosis, increased levels of serum TNF-alpha, IFN-gamma, IL-6, and liver proinflammatory cytokine mRNA expression. IFN-gamma, a cytokine sensitizing to endotoxin, was induced by P. acnes in splenocytes of TLR2-/- and TLR9-/- but not MyD88-/- mice. These results suggest that although P. acnes triggers TLR2-mediated cell activation, TLR2-independent but MyD88-dependent mechanisms mediate in vivo sensitization by P. acnes for LPS-induced liver injury.

In vitro and in vivo effects of an immunomodulator composed of Escherichia coli lipopolysaccharide and Propionibacterium granulosum-inactivated cells in pigs.

The in vitro cytokine profiles of porcine alveolar macrophages and peripheral blood mononuclear cells (PBMC) were examined by reverse transcription-polymerase chain reaction or enzyme-linked immunosorbent assay after stimulation with the immunomodulatory compound INMD [lipopolysaccharide (LPS) and Propionibacterium granulosum]. Expression of interleukin-1 (IL-1), IL-6, IL-12 and tumour necrosis factor-alpha (TNF-alpha), but not of IL-10, was detected in INMD-stimulated alveolar macrophages. Stimulated PBMC expressed IL-1, IL-2, IL-4, IL-6, IL-10 and IL-12 and secreted interferon-gamma (IFN-gamma). In all cases, the level of response was lower with INMD than with E. coli LPS alone, except for IFN-gamma, which was secreted in higher levels in INMD-stimulated cells. In a second experiment, the ex vivo effect of the administration of INMD was evaluated using the product as a coadjuvant of a live attenuated Aujeszky's disease virus (ADV) vaccine. For this purpose, 85 8-10-week-old crossbred pigs were assigned to two groups (group A = 43 and group B = 42) and vaccinated with ADV. Group B received, simultaneously with the first dose of vaccine, an intramuscular dose of INMD equivalent to 20 micrograms/ml LPS and 250 micrograms/ml P. granulosum, while group A was given sterile saline solution as a placebo. At the time of vaccination, 97.6% (42 of 43) and 95.2% (40 of 42) of animals of groups A and B, respectively, had anti-gB maternal antibodies. Of those animals, anti-gE ADV antibodies were detected in 11.6% of animals of group A (five of 43) and 19% of group B (eight of 42). All animals were boosted with ADV vaccine alone 4 weeks later. Pigs to which INMD was administered together with the vaccine showed higher primary humoral responses than the vaccine-alone animals (P < 0.005). However, after boosting significant differences disappeared (P > 0.05).

Effects of orally administered viable Lactobacillus rhamnosus GG and Propionibacterium freudenreichii subsp. shermanii JS on mouse lymphocyte proliferation.

Immunomodulation by probiotics is a subject of growing interest, but the knowledge of dose response and time profile relationships is minimal. In this study we examined the effects of Lactobacillus rhamnosus GG (LGG) and Propionibacterium freudenreichii subsp. shermanii JS (PJS) on the proliferative activity of murine lymphocytes ex vivo. Dose dependency was assessed by treating animals perorally with a low or a high dose (i.e., 10(9) or 10(12) viable bacteria/kg of body weight) for 7 days. The lower dose levels of each strain appeared to enhance T-cell proliferation at the optimal concanavalin A (ConA) concentration (by 69 to 84%) and B-cell proliferation at the optimal and supraoptimal concentrations of lipopolysaccharide (by 57 to 82%). B-cell proliferation was also enhanced by the high LGG dose (by 32 to 39%) but was accompanied by a marginal decrease in T-cell proliferation (by 8%) at the optimal ConA concentration. The time profiles of the immune responses were assessed after daily treatment with the higher dose for 3, 7, and 14 days. A significant decrease in basal lymphoproliferation (by 32 to 42%) was observed with PJS treatment after the 3- and 7-day periods; however, this activity returned to control levels after 14 days of treatment, which also resulted in significantly enhanced T-cell proliferation at optimal and supraoptimal ConA concentrations (by 24 to 80%). The 14-day LGG treatment also enhanced the latter activity (by 119%). In conclusion, LGG and PJS have specific dose- and duration-dependent immunomodulatory effects on the proliferative activity of B and T lymphocytes and may also reduce lymphocyte sensitivity to the cytotoxic effects of lectin mitogens.

Study of the morphology of the cell walls of some strains of lactic acid bacteria and related species.

The objective of the present study was to find an explanation for the biological effect of the bacteria present in a biotherapeutic milk (Lactobacillus casei CRL 431 and Lactobacillus acidophilus CRL 730). The ability of bacterial cell walls to induce an immune response when introduced into an organism is well known. In this paper we specifically analyzed the morphology of these cell walls. Besides the two bacterial strains used in the fermented milk, two other lactic acid bacteria, belonging to another genus and unable to induce an immune system response, as well as a strain of Propionibacterium, of which the immune modulating capacity is known, were used in this work. We found a structural particularly in strains with immunostimulating capacity (L. casei CRL 431 and P. acidopropionici CRL 1198): molecules which protrude from the cell surface. In L. casei CRL 431 these molecules were identified as lectins because they are able to agglutinate yeast cells treated with glutaraldehyde and glycine. The structures protruding from P. acidipropionici CRL 1198 cells were teichoic acids. Teichoic acid and lectin-like structures can participate in adhesion to intestinal cells. The immunostimulation observed can be induced by the adhesion phenomenon.

Protection and therapy of experimental herpesvirus infections in mice with immunomodulating Propionibacterium avidum KP-40 and/or acyclovir.

Protection and therapy of NMRI mice with experimental herpes virus (HSV-1) encephalitis were investigated using heat-killed, lyophilized Propionibacterium avidum KP-40 (PA) and/or the herpes-specific antiviral substance acyclovir (ACL) as immunomodifier. Poly I:C as a potent macrophage activator was used as a reference compound for PA. Survival of experimental HSV-1 infections during 18 days following the inoculation of viruses was used for the evaluation of the effects of immunotherapy. The applied model of HSV-1 infection resulted in a mortality of about 87% of NMRI mice at 7-16 days following the inoculation of the virus. Treatment with ACL or Poly I:C at the day of HSV-1 infection resulted in a lowering of the mortality rate to about 40% (p < 0.05). PA applied 4 days before HSV-1 infection lowered the mortality rate to 27%, while treatment 2 days after infection was less effective and the mortality rate reached 44%, although still being significantly lower (p < 0.01) than in untreated controls. A combined treatment with ACL and PA on the day of HSV-1 infection protected 93% of animals against the development of clinically detectable herpesvirus encephalitis.

Oral administration of a bacterial immunomodulator enhances the immune response to cholera toxin.

Attempts to achieve IgA responses in the intestine by oral immunization with non replicating antigens have been characterized by ineffective responses of short duration unless long term dosages are administered. Cholera toxin (CT) is an exception in that it is able to produce a high secretory and systemic immune response. We study the effects of a bacterial immunomodulator [3 x 10(10) Propionibacterium granulosum ml-1 and lipopolysaccharide (LPS) 5 mg ml-1] on the immune response to CT orally administered to Wistar rats. The immunomodulator was orally administered as follows: in schedule 1 during 7 days prior to the first dose of CT; and in schedule 2, 2 days before, together, and 3 days after the first dose of CT. Schedules 1 and 2 were effective in increasing the specific IgA in the intestinal fluid and specific IgG in serum (P < 0.001) when compared to controls. Besides, schedule 2 was more effective than schedule 1 when the levels of specific IgG in serum or specific IgA in intestinal fluid was measured (P < 0.05). Total IgA in the intestinal fluid was increased in rats receiving the immunomodulator (P < 0.01). However, the ratio of specific IgA per total IgA was higher in rats receiving treatment 1 or 2 when compared to controls (P < 0.01). The number of antitoxin antibody producing cells was not increased in the Peyer patches, but a significant increase was observed in the mesenteric lymph nodes and spleen when compared to controls (P < 0.05). The administration of LPS alone produced an increase in the antitoxin immune response when compared to controls, but it was lower than those produced by the administration of the immunomodulator. These results indicate that this immunomodulator is an effective adjuvant of the mucosal and systemic immune response to CT. The mechanisms of action possibly involve nonespecific and specific modulations of the immune response.

Influence of Propionibacterium avidum KP-40 on the cellular immune system after intensive sport activity.

Intensive sport activities resulted in temporary downregulation of defined immune functions. To check its influence on the cellular immune system, 15 male professional ice hockey players of a German first league club were observed and a decrease of lymphocyte subset counts and activities was found after anaerobic exercise. To stabilize cellular immune functions, the players were orally treated with Propionibacterium avidum KP-40 (10 mg per administration; twice a day; 7 days), a well documented bacterial immunmodifier. After administration of Propionibacterium avidum KP-40, lymphocyte counts and activities after anaerobic exercise resembled normal values. For some subjects, defined lymphocyte subset counts and activities even exceeded normal values.

Propionibacterium granulosum activities in rats during the muscle phase of Trichinella spiralis invasion.

Immune response of Wistar rats, infected with 4000 L1 T. spiralis and treated with P. granulosum during the muscle phase of nematode invasion were measured. The increase of spleen mass was observed in all groups infected and exposed to P. granulosum. Intraperitoneal injection of bacteria results in higher level of T lymphocytes and activated neutrophils. The level of inhibition of macrophages migration was depended on relation to the time and doses of injection. In non-specific stimulated animals there were not statistically significant changes in the level of specific IgG1 antibodies determined by ELISA, against the crude extract of infective larvae of T. spiralis. The reduction of intensity of nematode invasion during the muscle phase was not observed in rats after P. granulosum treatment.