Survey of Pathogen-Lowering and Immuno-Modulatory Effects Upon Treatment of Campylobacter coli-Infected Secondary Abiotic IL-10-/- Mice with the Probiotic Formulation Aviguard®

The prevalence of infections with the zoonotic enteritis pathogen Campylobacter coli is increasing. Probiotic formulations constitute promising antibiotic-independent approaches to reduce intestinal pathogen loads and modulate pathogen-induced immune responses in the infected human host, resulting in acute campylobacteriosis and post-infectious sequelae. Here, we address potential antipathogenic and immuno-modulatory effects of the commercial product Aviguard® during experimental campylobacteriosis. Secondary abiotic IL-10-/- mice were infected with a C. coli patient isolate on days 0 and 1, followed by oral Aviguard® treatment on days 2, 3 and 4. Until day 6 post-infection, Aviguard® treatment could lower the pathogen burdens within the proximal but not the distal intestinal tract. In contrast, the probiotic bacteria had sufficiently established in the intestines with lower fecal loads of obligate anaerobic species in C. coli-infected as compared to uninfected mice following Aviguard® treatment. Aviguard® application did not result in alleviated clinical signs, histopathological or apoptotic changes in the colon of infected IL-10-/- mice, whereas, however, Aviguard® treatment could dampen pathogen-induced innate and adaptive immune responses in the colon, accompanied by less distinct intestinal proinflammatory cytokine secretion. In conclusion, Aviguard® constitutes a promising probiotic compound to alleviate enteropathogen-induced proinflammatory immune responses during human campylobacteriosis.

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Diazepam Impairs Innate and Adaptive Immune Responses and Ameliorates Experimental Autoimmune Encephalomyelitis

Frontiers in Immunology ◽

10.3389/fimmu.2021.682612 ◽

2021 ◽

Vol 12 ◽

Author(s):

Cristian R. Falcón ◽

Nicolás Fernández Hurst ◽

Ana Laura Vivinetto ◽

Pablo Héctor Horacio López ◽

Adolfo Zurita ◽

...

Keyword(s):

Immune Responses ◽

Inflammatory Cytokine ◽

Cytokine Production ◽

Clinical Signs ◽

Autoimmune Encephalomyelitis ◽

Adaptive Immune Responses ◽

Inflammatory Cytokine Production ◽

Adaptive Immune ◽

Experimental Autoimmune

Currently there is increasing attention on the modulatory effects of benzodiazepines on the immune system. Here, we evaluate how Diazepam (DZ) affects both innate and adaptive immunity. We observed that treatment with DZ and Lipopolysaccharide (LPS) on macrophages or dendritic cells (DCs) induced a defective secretion of IL-12, TNF-α, IL-6 and a lesser expression of classical activation markers as NO production and CD40 in comparison with LPS condition. More importantly, mice pre-treated with DZ and then challenged to LPS induced-septic shock showed reduced death. The DZ treatment shifted the LPS-induced pro-inflammatory cytokine production of peritoneal cells (PCs) to an anti-inflammatory profile commanded by IL-10. In agreement with this, DZ treatment prevented LPS-induced DC ability to initiate allogeneic Th1 and Th17 responses in vitro when compared with LPS-matured DC. Since these inflammatory responses are the key in the development of the experimental autoimmune encephalomyelitis (EAE), we treated EAE mice preventively with DZ. Mice that received DZ showed amelioration of clinical signs and immunological parameters of the disease. Additionally, DZ reduced the release of IFN-γ and IL-17 by splenocytes from untreated sick mice in vitro. For this reason, we decided to treat diseased mice therapeutically with DZ when they reached the clinical score of 1. Most importantly, this treatment ameliorated clinical signs, reduced the MOG-specific inflammatory cytokine production and prevented axonal damage. Altogether, these results indicate that DZ is a potent immunomodulator capable of controlling undesired innate and adaptive immune responses, both at the beginning of these responses and also once they have started.

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Immune-modulatory Properties of the Octapeptide NAP in Campylobacter jejuni Infected Mice Suffering from Acute Enterocolitis

Microorganisms ◽

10.3390/microorganisms8060802 ◽

2020 ◽

Vol 8 (6) ◽

pp. 802 ◽

Cited By ~ 3

Author(s):

Markus M. Heimesaat ◽

Soraya Mousavi ◽

Sigri Kløve ◽

Claudia Genger ◽

Dennis Weschka ◽

...

Keyword(s):

Immune Responses ◽

Campylobacter Jejuni ◽

Post Infection ◽

Intestinal Tract ◽

Clinical Signs ◽

Global Public Health ◽

Food Borne ◽

Human Infections ◽

First Time ◽

Post Infectious

Human infections with the food-borne zoonotic pathogen Campylobacter jejuni are progressively rising and constitute serious global public health and socioeconomic burdens. Hence, application of compounds with disease-alleviating properties are required to combat campylobacteriosis and post-infectious sequelae. In our preclinical intervention study applying an acute C. jejuni induced enterocolitis model, we surveyed the anti-pathogenic and immune-modulatory effects of the octapeptide NAP which is well-known for its neuroprotective and anti-inflammatory properties. Therefore, secondary abiotic IL-10−/− mice were perorally infected with C. jejuni and intraperitoneally treated with synthetic NAP from day 2 until day 5 post-infection. NAP-treatment did not affect gastrointestinal C. jejuni colonization but could alleviate clinical signs of infection that was accompanied by less pronounced apoptosis of colonic epithelial cells and enhancement of cell regenerative measures on day 6 post-infection. Moreover, NAP-treatment resulted in less distinct innate and adaptive pro-inflammatory immune responses that were not restricted to the intestinal tract but could also be observed in extra-intestinal and even systemic compartments. NAP-treatment further resulted in less frequent translocation of viable pathogens from the intestinal tract to extra-intestinal including systemic tissue sites. For the first time, we here provide evidence that NAP application constitutes a promising option to combat acute campylobacteriosis.

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