Oral and Intraperitoneal Administration of Phosphorothioate Oligodeoxynucleotides Leads to Control of<i>Cryptosporidium parvum</i>Infection in Neonatal Mice

Barrier, Mathieu; Lacroix‐Lamandé, Sonia; Mancassola, Roselyne; Auray, Gaël; Bernardet, Nelly; Chaussé, Anne-Marie; Uematsu, Satoshi; Akira, Shizuo; Laurent, Fabrice

doi:10.1086/503748

Cited by 54 publications

(43 citation statements)

References 35 publications

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“…For the first time, we demonstrate the development of both high T h 1 and T h 17 function in the neonatal intestine to a fully virulent infectious bacterium in the absence of additional interventions. Based on the current understanding that immune responsiveness during the neonatal period of life can be modulated extensively by targeting the mucosal immune system (1,8,11,12,27,29,34,35,59,70) and by using strong immunomodulatory agents (31,36,51), we favor the idea that robust immunity to Y. enterocolitica is a function of both the inflammatory potential of this pathogen and an intrinsic capacity of the neonatal intestine to develop high-level inflammation. These data support the idea that the development of inflammatory CD4…”

Section: Discussionmentioning

confidence: 99%

“…For example, bacterially derived products such as mutated Escherichia coli enterotoxins LT-R192G (70) and LT-K63 (11,14,27,34), CpG oligonucleotides (CpG) (8,29,31), and lyophilized bacterial extracts (12) have been described to markedly enhance neonatal vaccine responses. Another approach used to improve immune responses has been the delivery of specific antigens using live attenuated bacterial vectors such as Listeria monocytogenes (42,50) and Salmonella species (16,59).…”

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confidence: 99%

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Yersinia enterocoliticaPromotes Robust Mucosal Inflammatory T-Cell Immunity in Murine Neonates

et al. 2010

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Yersinia enterocoliticaPromotes Robust Mucosal Inflammatory T-Cell Immunity in Murine Neonates

et al. 2010

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“…Further, in Toxoplasma, a TLR9 response that contributed to T H 1 development depended on bacterial antigens (12). Similarly, neonatal mice fed TLR9 agonists had an enhanced T H 1 response after a Cryptosporidium challenge (13).…”

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confidence: 98%

Fecal Indole as a Biomarker of Susceptibility to Cryptosporidium Infection

et al. 2016

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e Cryptosporidium causes significant diarrhea worldwide, especially among children and immunocompromised individuals, and no effective drug treatment is currently available for those who need it most. In this report, previous volunteer infectivity studies have been extended to examine the association between fecal indole and indole-producing (IP) gut microbiota on the outcome of a Cryptosporidium infection. Fecal indole concentrations (FICs) of 50 subjects and 19 taxa of common gut microbiota, including six IP taxa (11 subjects) were determined in stool samples collected before and after a challenge with Cryptosporidium oocysts. At the baseline, the mean FIC (؎ the standard deviation) was 1.66 ؎ 0.80 mM in those who became infected after a challenge versus 3.20 ؎ 1.23 mM in those who remained uninfected (P ‫؍‬ 0.0001). Only 11.1% of the subjects with a FIC of >2.5 mM became infected after a challenge versus 65.2% of the subjects with a FIC of <2.5 mM. In contrast, the FICs of infected subjects at the baseline or during diarrhea were not correlated with infection intensity or disease severity. The relative abundances (percent) of Escherichia coli, Bacillus spp., and Clostridium spp. were greater >2.5-fold in volunteers with a baseline FIC of >2.5 mM, while those of Bacteroides pyogenes, B. fragilis, and Akkermansia muciniphila were greater in those with a baseline FIC of <2.5 mM. These data indicate that some IP bacteria, or perhaps indole alone, can influence the ability of Cryptosporidium to establish an infection. Thus, preexisting indole levels in the gut join the oocyst dose and immune status as important factors that determine the outcome of Cryptosporidium exposure.

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“…Several Toll-like receptors (TLRs) are associated with protection against infection (2,24,25,41). The adaptive immune response to Cryptosporidium is characterized as a T-helper 1 (Th1) response with significant contribution of IL-12, IL-18, IL-23, and gamma interferon (IFN-␥) to the clearance of infection (8).…”

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confidence: 99%

Identification and Immunological Characterization of Three Potential Vaccinogens against Cryptosporidium Species

Manque

Tenjo

Woehlbier

et al. 2011

Clin Vaccine Immunol

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Cryptosporidiosis is a ubiquitous infectious disease, caused by the protozoan parasites Cryptosporidium hominis and Cryptosporidium parvum, leading to acute, persistent, and chronic diarrhea with life-threatening consequences in immunocompromised individuals. In developing countries, cryptosporidiosis in early childhood has been associated with subsequent significant impairment in growth, physical fitness, and intellectual abilities. Currently, vaccines are unavailable and chemotherapeutics are toxic and impractical, and agents for immunoprophylaxis or treatment of cryptosporidiosis are a high priority. Availability of the genome sequences for C. hominis and C. parvum provides new opportunities to procure and examine novel vaccine candidates. Using the novel approach of "reverse vaccinology," we identified several new potential vaccine candidates. Three of these antigens-Cp15, profilin, and a Cryptosporidium apyrase-were delivered in heterologous prime-boost regimens as fusions with cytolysin A (ClyA) in a Salmonella live vaccine vector and as purified recombinant antigens, and they were found to induce specific and potent humoral and cellular immune responses, suggesting their potential as new vaccinogens against Cryptosporidium infection.

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Oral and Intraperitoneal Administration of Phosphorothioate Oligodeoxynucleotides Leads to Control ofCryptosporidium parvumInfection in Neonatal Mice

Cited by 54 publications

References 35 publications

Yersinia enterocoliticaPromotes Robust Mucosal Inflammatory T-Cell Immunity in Murine Neonates

Yersinia enterocoliticaPromotes Robust Mucosal Inflammatory T-Cell Immunity in Murine Neonates

Fecal Indole as a Biomarker of Susceptibility to Cryptosporidium Infection

Identification and Immunological Characterization of Three Potential Vaccinogens against Cryptosporidium Species

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