scholarly journals Enhancing mucosal immunity by transient microbiota depletion

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Simone Becattini ◽  
Eric R. Littmann ◽  
Ruth Seok ◽  
Luigi Amoretti ◽  
Emily Fontana ◽  
...  
Keyword(s):  
Intestinal Tract ◽  
Infectious Agents ◽  
Colonization Resistance ◽  
Mucosal Vaccination ◽  
Mucosal Surfaces ◽  
Pathogen Entry ◽  
Portal Of Entry ◽  
Optimal Protection ◽  
Antigenic Load ◽  
Chemotactic Gradient

Abstract Tissue resident memory CD8+ T cells (Trm) are poised for immediate reactivation at sites of pathogen entry and provide optimal protection of mucosal surfaces. The intestinal tract represents a portal of entry for many infectious agents; however, to date specific strategies to enhance Trm responses at this site are lacking. Here, we present TMDI (Transient Microbiota Depletion-boosted Immunization), an approach that leverages antibiotic treatment to temporarily restrain microbiota-mediated colonization resistance, and favor intestinal expansion to high densities of an orally-delivered Listeria monocytogenes strain carrying an antigen of choice. By augmenting the local chemotactic gradient as well as the antigenic load, this procedure generates a highly expanded pool of functional, antigen-specific intestinal Trm, ultimately enhancing protection against infectious re-challenge in mice. We propose that TMDI is a useful model to dissect the requirements for optimal Trm responses in the intestine, and also a potential platform to devise novel mucosal vaccination approaches.

Meningoencephalomyelitis in domestic cats: 3 cases of Pasteurella multocida infection and literature review

2021 ◽  
pp. 104063872110344
Author(s):  
Bianca S. de Cecco ◽  
Mariano Carossino ◽  
Fabio Del Piero ◽  
Nobuko Wakamatsu ◽  
Maria S. Mitchell ◽  
...  
Keyword(s):  
Pasteurella Multocida ◽  
Case Series ◽  
Infectious Agents ◽  
Domestic Cats ◽  
Neurologic Diseases ◽  
Gram Negative ◽  
The Central Nervous System ◽  
Upper Respiratory ◽  
Portal Of Entry ◽  
Histologic Changes

Neurologic diseases are common in domestic cats, and infectious agents are suspected to be the primary cause in 30–45% of cases. Among infectious etiologies, those of bacterial origin are only sporadically characterized in the literature, with few of these reports correlating gross and histologic findings with confirmatory bacteriologic identification. Here, we describe bacterial meningitis and meningoencephalomyelitis associated with Pasteurella multocida in 3 domestic cats. Purulent exudate expanding the cerebral meninges was grossly evident in 2 of the cases. In all 3 cases, histologic changes included multifocal suppurative-to-necrosuppurative meningitis and/or meningoencephalomyelitis of variable severity. Intralesional colonies of gram-negative, short rod-shaped to coccobacillary bacteria were evident histologically in only 1 case. P. multocida was confirmed by routine bacteriologic culture in all cases. Based on our cases, we hypothesize that the upper respiratory system serves as the main portal of entry for P. multocida, leading to invasion of the central nervous system and possible systemic hematogenous dissemination. A case series of meningoencephalomyelitis associated with P. multocida infection in cats has not been reported previously, to our knowledge. We also review briefly other causes of meningoencephalomyelitis in cats.

scholarly journals Colonization resistance of the digestive tract in conventional and antibiotic-treated mice

1971 ◽  
Vol 69 (3) ◽  
pp. 405-411 ◽  
Author(s):  
D. Van der Waaij ◽  
J. M. Berghuis-de Vries ◽  
J. E. C. Lekkerkerk-van der Wees
Keyword(s):  
Escherichia Coli ◽  
Pseudomonas Aeruginosa ◽  
Intestinal Tract ◽  
Normal Values ◽  
Anaerobic Bacteria ◽  
Intestinal Flora ◽  
Treated Animal ◽  
Housing Conditions ◽  
Colonization Resistance ◽  
Germ Free

SUMMARYThe effect of oral administration of antibiotics on the intestinal flora of conventional mice and their resistance to colonization by orally introducedEscherichia coli, Klebsiella pneumoniaeandPseudomonas aeruginosawas studied. Colonization resistance (CR) was expressed as the log of the oral bacterial dose followed by a persistent take in 50 % of the contaminated animals. The intestinal flora was virtually eliminated by the antibiotics and this elimination was accompanied by a precipitous fall of CR. CR gradually returned to normal values during the period of repopulation of the intestinal tract by the organisms surviving the treatment. Antibiotic treatment resulted in the disappearance of Enterobacteriaceae, enterococci, staphylococci and yeasts and, under appropriate housing conditions, the animals remained free of these organisms indefinitely. Germ-free mice contaminated with the intestinal flora of an antibiotic-treated animal and their offspring housed in a germ-free isolator showed high values of CR. Their intestinal flora consisted of anaerobic bacteria only. Apparently, these anaerobes are responsible for CR in these and in conventional mice.

Aspects of Immunology of the Gut and Rotavirus Infection

1993 ◽  
Vol 1993 ◽  
pp. 32-32
Author(s):  
Geoffrey Oldham
Keyword(s):  
Immune Responses ◽  
Mucosal Immunity ◽  
Mucosal Surface ◽  
Pathogenic Microorganisms ◽  
Subsequent Infection ◽  
Mucosal Surfaces ◽  
Artificial Induction ◽  
Enteric Infections ◽  
Portal Of Entry ◽  
Immune Defences

The major portal of entry for most pathogenic microorganisms is the mucosal surface. It seems reasonable therefore that the host in its turn should possess substantial immune defences at the mucosae to provide protection against these insults. Enteric infections usually result in at least some degree of specific protection against a subsequent infection with the same organism. However artificial induction of mucosal immunity has proved difficult. Clearly, as yet, we do not have a full understanding of the inductive events involved in the generation of mucosal immune responses or the immune mechanisms operating at mucosal surfaces. In this paper I will attempt to briefly review the main aspects of mucosal immunity concentrating on the gut as the model mucosal surface.

scholarly journals Host–microflora interaction in Systemic Lupus Erythematosus (SLE): colonization resistance of the indigenous bacteria of the intestinal tract

1994 ◽  
Vol 112 (2) ◽  
pp. 367-373 ◽  
Author(s):  
H. Z. Apperloo-Renkema ◽  
H. Bootsma ◽  
B. I. Mulder ◽  
C. G. Kallenberg ◽  
D. Van Der Waaij
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Antibody Production ◽  
Lupus Erythematosus ◽  
Intestinal Tract ◽  
Healthy Individuals ◽  
Colonization Resistance ◽  
Systemic Lupus ◽  
Dna Antibodies ◽  
Translocation Of Bacteria ◽  
Indigenous Microflora

SUMMARYExperimental data suggest a role for the microflora in Systemic Lupus Erythematosus (SLE). Anti–ds–DNA antibodies may be pathogenic in SLE by forming immune complexes with DNA. Foreign bacteria in the intestines could constitute the stimulus for anti–ds–DNA antibody production in SLE. Colonization Resistance (CR) is the defence capacity of the indigenous microflora against colonization of the intestines by foreign bacteria. A low CR implies increase of translocation of bacteria and a higher chance of subsequent, possibly DNA–cross–reacting antibacterial antibody production.We measured CR by a comprehensive biotyping technique in healthy individuals and patients with inactive and active SLE. CR tended to be lower in active SLE patients than in healthy individuals (P = 0.09, Wilcoxon one sided, with correction for ties). This could indicate that in SLE more and different bacteria translocate across the gut wall due to a lower CR. Some of these may serve as polyconal B cell activators or as antigens cross-reacting with DNA.

scholarly journals Candida glabrata colonizes but does not often disseminate from the mouse caecum

2007 ◽  
Vol 56 (5) ◽  
pp. 688-693 ◽  
Author(s):  
Carol L. Wells ◽  
Mary-Alice Johnson ◽  
Michelle J. Henry-Stanley ◽  
Catherine M. Bendel
Keyword(s):  
Candida Albicans ◽  
Candida Glabrata ◽  
Intestinal Tract ◽  
Systemic Candidiasis ◽  
Intestinal Microbes ◽  
Oral Inoculation ◽  
Mouse Intestine ◽  
High Doses ◽  
Clinical Conditions ◽  
Portal Of Entry

Candida glabrata is the second or third most frequent cause of candidaemia. The gastrointestinal tract is considered to be a major portal of entry for systemic candidiasis, but relatively few studies have investigated the pathogenesis of C. glabrata. Experiments were designed to clarify the ability of C. glabrata to disseminate from the mouse intestinal tract. Following oral inoculation, C. glabrata readily colonized the caeca [approx. 107 cells (g caecum)−1] of antibiotic-treated mice, but extraintestinal dissemination was not detected. Superimposing several mouse models of trauma and/or immunosuppression known to induce dissemination of Candida albicans and other intestinal microbes did not cause C. glabrata to disseminate often, although one exception was mice given high doses of dexamethasone for 4 days. These data support the hypothesis that the antibiotic-treated mouse intestine may be an epidemiological reservoir for C. glabrata and that this yeast tends to disseminate under specific clinical conditions.

scholarly journals Enhancement of Protective Efficacy following Intranasal Immunization with Vaccine Plus a Nontoxic LTK63 Mutant Delivered with Nanoparticles

2002 ◽  
Vol 70 (9) ◽  
pp. 4785-4790 ◽  
Author(s):  
B. C. Baudner ◽  
O. Balland ◽  
M. M. Giuliani ◽  
P. Von Hoegen ◽  
R. Rappuoli ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Protective Efficacy ◽  
Vaccination Strategy ◽  
Meningococcal Vaccine ◽  
Intranasal Immunization ◽  
Mucosal Vaccination ◽  
Parenteral Immunization ◽  
Encapsulated Bacteria ◽  
Portal Of Entry ◽  
Very High

ABSTRACT Most vaccines are still given parenterally. Mucosal vaccination would offer different advantages over parenteral immunization, including blocking of the pathogens at the portal of entry. In this paper, nontoxic Escherichia coli heat-labile enterotoxin (LT) mutants and Supramolecular Biovector systems (SMBV) were evaluated in mice as mucosal adjuvants and delivery systems, respectively, for intranasal immunization with the conjugated group C meningococcal vaccine. The conjugated vaccine formulated together with the LT mutants and the SMBV induced very high titers of serum and mucosal antibodies specific for the group C meningococcal polysaccharide. This vaccination strategy also induced high titers of antibodies with bactericidal activity, which is known to correlate with efficacy. Importantly, the mucosal vaccination, but not the conventional parenteral vaccination, induced bactericidal antibodies at the mucosal level. These data strongly support the feasibility of development of intranasal vaccines with an enhanced protective efficacy against meningococci and possibly against other encapsulated bacteria.

Advances in mucosal vaccination

2004 ◽  
Vol 5 (2) ◽  
pp. 209-217 ◽  
Author(s):  
Els N. T. Meeusen ◽  
Jean-Pierre Y. Scheerlinck ◽  
Sean Wattegedera ◽  
Gary Entrican
Keyword(s):  
Defense Mechanisms ◽  
Management Practices ◽  
The Body ◽  
Secretory Iga ◽  
Specific Reference ◽  
Small Rodent ◽  
Mucosal Vaccination ◽  
Complex Interactions ◽  
Mucosal Surfaces ◽  
Large Animals

AbstractPathogens that enter the body via mucosal surfaces face unique defense mechanisms that combine the innate barrier provided by the mucus layer with an adaptive response typified by the production and transepithelial secretion of pathogen-specific IgA. Both the measurement and induction of mucosal responses pose significant challenges for experimental and practical application and may need to be adapted to the species under study. In particular, for livestock, immunization procedures developed in small rodent models are not always effective in large animals or compatible with management practices. This paper reviews the latest advances in our understanding of the processes that lead to secretory IgA responses and how this relates to the development of mucosal immunization procedures and adjuvants for veterinary vaccines. In addition, it highlights the complex interactions that can take place between the pathogen and the host's immune response, with specific reference toChlamydia/Chlamydophilainfections in sheep.

scholarly journals COVID-19: A Recommendation to Examine the Effect of Mouthrinses with β-Cyclodextrin Combined with Citrox in Preventing Infection and Progression

2020 ◽  
Vol 9 (4) ◽  
pp. 1126 ◽  
Author(s):  
Florence Carrouel ◽  
Maria Pia Conte ◽  
Julian Fisher ◽  
Lucio Souza Gonçalves ◽  
Claude Dussart ◽  
...  
Keyword(s):  
Viral Load ◽  
Evolutionary Process ◽  
Adjunctive Treatment ◽  
Infectious Agents ◽  
Oral Biofilm ◽  
Ambient Particles ◽  
Oral Transmission ◽  
Mouth Rinses ◽  
Portal Of Entry ◽  
Preventive Effects

Considered to be a major portal of entry for infectious agents, the oral cavity is directly associated with the evolutionary process of SARS-CoV-2 in its inhalation of ambient particles in the air and in expectorations. Some new generations of mouth rinses currently on the market have ingredients that could contribute to lower the SARS-CoV-2 viral load, and thus facilitate the fight against oral transmission. If chlorhexidine, a usual component of mouth rinse, is not efficient to kill SARS-CoV-2, the use of a mouth rinses and/or with local nasal applications that contain β-cyclodextrins combined with flavonoids agents, such as Citrox, could provide valuable adjunctive treatment to reduce the viral load of saliva and nasopharyngeal microbiota, including potential SARS-CoV-2 carriage. We urge national agencies and authorities to start clinical trials to evaluate the preventive effects of βCD-Citrox therapeutic oral biofilm rinses in reducing the viral load of the infection and possibly disease progression.

scholarly journals Oral DAV131, a Charcoal-Based Adsorbent, Inhibits Intestinal Colonization by β-Lactam-Resistant Klebsiella pneumoniae in Cefotaxime-Treated Mice

2013 ◽  
Vol 57 (11) ◽  
pp. 5423-5425 ◽  
Author(s):  
Nathalie Grall ◽  
Laurent Massias ◽  
Thu Thuy Nguyen ◽  
Sakina Sayah-Jeanne ◽  
Nicolas Ducrot ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Intestinal Tract ◽  
Area Under The Curve ◽  
Resistant Bacteria ◽  
Intestinal Colonization ◽  
Colonization Resistance ◽  
Content Type ◽  
Resistant Strains ◽  
The Impact ◽  
Indigenous Microflora

ABSTRACTAntibiotics excreted into the intestinal tract, such as broad-spectrum cephalosporins, disrupt the indigenous microflora, affect colonization resistance (CR), and promote intestinal colonization by resistant bacteria. We tested whether oral DAV131, a charcoal-based adsorbent, would prevent colonization by a cefotaxime (CTX)-resistantKlebsiella pneumoniaestrain (PUG-2) in CTX-treated mice. Mice received CTX, saline, CTX and DAV131, or saline and DAV131 for 3 days before oral challenge with 106CFU of PUG-2. The fecal CTX concentrations and counts of PUG-2 were assayed. Fecal CTX disappeared when DAV131 was given concomitantly with CTX (P< 0.05), and the area under the curve of PUG-2 fecal density was significantly reduced (P< 0.01). In conclusion, reducing intestinal antibiotic exposure with DAV131 may reduce colonization by resistant strains during treatment compared to treatment with CTX only. This might open new possibilities for decreasing the impact of antibiotics on the intestinal microbiota during treatments.

scholarly journals Permanent Colonization by Lactobacillus casei Is Hindered by the Low Rate of Cell Division in Mouse Gut

2004 ◽  
Vol 70 (2) ◽  
pp. 670-674 ◽  
Author(s):  
Y. K. Lee ◽  
P. S. Ho ◽  
C. S. Low ◽  
H. Arvilommi ◽  
S. Salminen
Keyword(s):  
Lactobacillus Casei ◽  
Doubling Time ◽  
Intestinal Tract ◽  
Mucosal Surfaces ◽  
Colonization Potential ◽  
Mouse Intestine ◽  
Succinimidyl Ester ◽  
Doubling Times ◽  
Average Doubling Time ◽  
Different Parts

ABSTRACT Long residence times of probiotics in the intestinal tract would prolong their potential beneficial health effects and assist colonization. This study investigated the colonization potential of Lactobacillus casei Shirota in mouse intestine by using 5 (and 6)-carboxyfluorescein diacetate, succinimidyl ester (cFDA-SE) for assessment of doubling times in different parts of the intestine. The amounts of intestinal water overlying the surfaces of the duodenum, jejunum, ileum, and colon in BALB/c mice were 34.4 ± 2.9, 58.8 ± 6.8, 21.6 ± 2.2, and 8.0 ± 1.0 mg, respectively. Based on the residual concentrations of cFDA-SE-labeled lactobacilli on intestinal mucosal surfaces, the average half times for the wash-out of lactobacilli fed were estimated at 3.98, 1.55, 1.34, and 2.48 days in the duodenum, jejunum, ileum, and colon, respectively. The average doubling times of the lactobacilli, estimated from the residual fluorescent levels of surface-adhered cells, were 4.10, 4.78, 4.56, and 5.59 days in the duodenum, jejunum, ileum, and colon, respectively. It is estimated that the lactobacilli would have to achieve an average doubling time of 1.03 to 2.04 days to colonize the various sections of the mouse intestinal tract more permanently.

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