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

Autor: Fabrice Laurent, Anne-Marie Chaussé, Satoshi Uematsu, Sonia Lacroix-Lamandé, Shizuo Akira, Nelly Bernardet, Mathieu Barrier, Gaël Auray, Roselyne Mancassola
Přispěvatelé: Infectiologie Animale et Santé Publique (UR IASP), Institut National de la Recherche Agronomique (INRA), Osaka University [Osaka]
Rok vydání: 2006
Předmět:
Male
[SDV]Life Sciences [q-bio]
medicine.medical_treatment
Administration
Oral

Cryptosporidiosis
ADJUVANT
Polymerase Chain Reaction
Parasite load
Mice
MOTIFS
0302 clinical medicine
Parasitic Sensitivity Tests
Oral administration
Immunology and Allergy
PROTECTION
IMMUNE-RESPONSES T-LYMPHOCYTES
Mice
Knockout

Mice
Inbred BALB C

0303 health sciences
biology
hemic and immune systems
respiratory system
Specific Pathogen-Free Organisms
3. Good health
CPG OLIGODEOXYNUCLEOTIDES GAMMA-INTERFERON BACTERIAL-DNA
Infectious Diseases
Cryptosporidium parvum
Cytokine
Oligodeoxyribonucleotides
CpG site
Female
Injections
Intraperitoneal

RNA
Protozoan

EXPRESSION
CpG Oligodeoxynucleotide
Drug Administration Schedule
03 medical and health sciences
Immune system
Adjuvants
Immunologic

medicine
Animals
Humans
030304 developmental biology
IMMUNOCOMPETENT
TLR9
biology.organism_classification
Mice
Inbred C57BL

Disease Models
Animal

Animals
Newborn

Immunology
030215 immunology
Zdroj: HAL
Journal of Infectious Diseases
Journal of Infectious Diseases, Oxford University Press (OUP), 2006, 193 (10), pp.1400-1407. ⟨10.1086/503748⟩
ISSN: 1537-6613
0022-1899
Popis: International audience; Background. Neonates are particularly vulnerable to infections, in part because of the incomplete development of their immune system. Recent advances in immunostimulatory treatments based on conserved microbial components led us to assess the potential of oligodeoxynucleotides ( ODNs) for decreasing the sensitivity of neonates to Cryptosporidium parvum infection. Methods. Neonate mice were treated orally or intraperitoneally ( ip) with CpG ODNs or non-CpG ODNs 24 h before C. parvum infection, and parasite load and cytokine up-regulation were evaluated. Results. CpG ODN 1668 and non-CpG ODN 1668 administered orally, as well as CpG ODN 1668 administered ip, induced an 80%-95% decrease in intestinal parasite load 6 days after infection. Intraperitoneal and oral pretreatment with CpG ODN 1668 led to a strong initial up-regulation of cytokines and CD69 messenger RNA in the intestine and a decrease in parasite load by a Toll-like receptor 9 ( TLR9)-dependent mechanism. By contrast, oral administration of non-CpG ODN 1668 decreased parasite load by a TLR9-independent mechanism. Conclusion. The control of neonatal C. parvum infection by ip or oral administration of ODNs is feasible by 2 different mechanisms: ( 1) the well-known interaction involving CpG/TLR9, leading to the production of cytokines and lymphocyte activation, and ( 2) a new unknown mechanism that is independent of TLR9 and effective orally.
Databáze: OpenAIRE