Differential expression of sheep beta-defensin-1 and -2 and interleukin 8 during acute Mannheimia haemolytica pneumonia

Abstract

Beta-defensins are antimicrobial peptides produced by several cell types, including respiratory epithelia and leukocytes. Expression of some beta-defensins is increased by bacterial-induced inflammatory responses whereas expression of other beta-defensins is constitutive. Two beta-defensins are expressed in lungs of sheep (sheep beta-defensin-1 and -2; SBD-1/-2) and expression of SBD-1 is increased during parainfluenza virus type 3 (PI-3) infection. The effect of Mannheimia haemolytica, a Gram-negative bacteria known to induce expression of bovine beta-defensins and NF-kappa B in lung, has not been determined for SBD-1/-2. In this study, different concentrations of M. haemolytica were inoculated into pulmonary bronchi of lambs. SBD-1 and SBD-2 mRNA levels detected by real time reverse transcriptase polymerase chain reaction in lung homogenates did not increase. In fact, SBD-1 mRNA levels were significantly decreased with the highest administered inoculum concentration (10 9 ). In contrast, mRNA levels of interleukin-8 (IL-8) were significantly increased over controls and progressively increased with M. haemolytica concentrations. Coinoculation of M. haemolytica with xylitol, an osmotic agent, did not alter mRNA levels of SBD-1, SBD-2 or IL-8. SBD-1 mRNA expression was detected in lung epithelia, but not in leukocytes. This study suggests that SDB-1 expression occurs in epithelia and decreases during severe bacterial pneumonia, which is in contrast to the increase that occurs with PI-3 infection. RightsWorks produced by employees of the U.S. Government as part of their official duties are not copyrighted within the U.S. The content of this document is not copyrighted. AuthorsMark R. Ackermann, Jack M. Abstract Beta-defensins are antimicrobial peptides produced by several cell types, including respiratory epithelia and leukocytes. Expression of some beta-defensins is increased by bacterial-induced inflammatory responses whereas expression of other beta-defensins is constitutive. Two beta-defensins are expressed in lungs of sheep (sheep beta-defensin-1 and -2; SBD-1/-2) and expression of SBD-1 is increased during parainfluenza virus type 3 (PI-3) infection. The effect of Mannheimia haemolytica, a Gram-negative bacteria known to induce expression of bovine beta-defensins and NF-kappa B in lung, has not been determined for SBD-1/-2. In this study, different concentrations of M. haemolytica were inoculated into pulmonary bronchi of lambs. SBD-1 and SBD-2 mRNA levels detected by real time reverse transcriptase polymerase chain reaction in lung homogenates did not increase. In fact, SBD-1 mRNA levels were significantly decreased with the highest administered inoculum concentration (10 9 ). In contrast, mRNA levels of interleukin-8 (IL-8) were significantly increased over controls and progressively increased with M. haemolytica concentrations. Co-inoculation of M. haemolytica with xylitol, an osmotic agent, did not alter mRNA levels of SBD-1, SBD-2 or IL-8. SBD-1 mRNA expression was detected in lung epithelia, b...

Expression of select immune genes (surfactant proteins A and D, sheep beta defensin 1, and toll-like receptor 4) by respiratory epithelia is developmentally regulated in the preterm neonatal lamb

“…This trend corresponded with previous work, which identified terminal airway (e.g. bronchiolar) epithelium as a major site of SBD1 expression compared to bronchial epithelium [16]. In this current study we were not able to show statistically significant alterations in specific cell lineages suggesting CD208+, CD208− and possibly other cell types collectively contribute to the innate immune expression of beta-defensins in the developing ovine lung.…”

“…SBD1). This is similar to previous work in which LCM-retrieved bronchiolar epithelium showed significantly more SBD1 expression than whole lung homogenates [16]. Furthermore, the current study further characterizes the BAJ as a richer site of SBD1 developmental expression than bronchial epithelium.…”

“…In this current study we were not able to show statistically significant alterations in specific cell lineages suggesting CD208+, CD208− and possibly other cell types collectively contribute to the innate immune expression of beta-defensins in the developing ovine lung. While this study demonstrates developmental regulation of SBD1 mRNA in BAJ epithelium, SBD1 regulation appears to be complex with increased expression seen during clearance of PIV3 infection, but there is reduced expression following Mannheimia hemolytica inoculation [10,16].…”

“…They have also been useful for study of RSV, parainfluenza virus-3 (PIV-3) infection and other infectious respiratory diseases [10,14]. Sheep infected with ovine RSV strains have consistency with human RSV disease including increased susceptibility in newborns, lesions, and similar innate immune genes [15][16][17]. Recently, preterm lambs were shown to have reduced RSV clearance compared to full-term lambs, which is similar to age-dependent disease seen in preterm RSV infected infants [2,3,15].…”

Immunity in the female sheep reproductive tract

“…Similar to the expression pattern of HBD-1, SBD-1 is constitutively expressed in epithelial cells throughout the gastrointestinal tract. SBD-2 is expressed in the gut, lung and uterus [3,56]. It is not yet possible to say if and how SBD-1 or -2 contribute to innate immune defence in the reproductive tract of sheep or how their expression is regulated.…”