Paneth cell alpha-defensins from rhesus macaque small intestine

Area of Science:

• Immunology
• Gastroenterology
• Molecular Biology

Background:

• Antimicrobial peptides, such as alpha-defensins, are vital components of the innate immune system.
• Paneth cells in the small intestine secrete these peptides to maintain gut homeostasis.
• Understanding enteric alpha-defensins in primates is crucial for elucidating host defense mechanisms.

Purpose of the Study:

• To investigate the role and characteristics of alpha-defensins in nonhuman primate enteric host defenses.
• To identify and characterize rhesus enteric alpha-defensins (REDs) and their antimicrobial activities.

Main Methods:

• Isolation of alpha-defensin cDNAs from rhesus macaque jejunum.
• Purification of alpha-defensin peptides from rhesus macaque small bowel.
• Measurement of bactericidal activities of purified peptides against various bacteria.
• In situ hybridization to determine the cellular localization of RED mRNAs.

Main Results:

• Six novel rhesus enteric alpha-defensin (RED) cDNAs (RED-1 to RED-6) were identified, showing significant structural diversity compared to myeloid alpha-defensins.
• RED-4 peptides exhibited two alternative N-termini, confirmed by peptide sequencing and molecular mass analysis.
• RED mRNAs were exclusively localized to small intestinal Paneth cells.
• Purified recombinant RED-1 to RED-4 demonstrated microbicidal activity against Gram-positive and Gram-negative bacteria, with variable specificities.

Conclusions:

• Enteric alpha-defensin peptides in rhesus macaques display substantial variability in primary structure and antimicrobial function.
• These findings highlight the diverse nature of alpha-defensins in primate enteric immunity.
• The characterized REDs provide a foundation for further research into their specific roles in host defense.