Developmental expression of Toll-like receptors in the guinea pig lung

Abstract

The guinea pig is a useful model for investigating infectious and non-infectious lung diseases due to the sensitivity of its respiratory system and susceptibility to infectious agents. Toll-like receptors (TLRs) are important components of the innate immune response and are critical for lung immune function. In the present study, the differentiation of epithelial cells in the guinea pig lung was examined during gestation by studying anatomic morphology and the major epithelial cell types using cell type-specific markers. The developmental expression of all 9 TLRs and the TLR signaling adaptors myeloid differentiation factor 88 (MyD88) and tumor necrosis factor receptor associated factor 6 (TRAF-6) were investigated by reverse transcription-quantitative polymerase chain reaction and western blotting analysis. The formation of lung lobes in guinea pigs was observed at 45 days of gestation (dGA), along with the expression of the basal cell marker keratin 14 and the alveolar type II cell marker pro-surfactant protein. However, the cube cell marker secretoglobin family1A member 1 and ciliated cell marker b-tubulin IV were only detected in the lungs from 52 dGA onward. The expression levels of all TLRs, MyD88 and TRAF-6 were determined in lung tissues harvested from embryos, newborn, postnatal and adult animals. The expression levels of all TLR signaling components displayed similar dynamic expression patterns with gestation age and postnatal maturation time, except for TLR-4 and TLR-7. mRNA expression levels of TLR components were significantly increased in the lungs at 45 and 52 dGA, compared with later developmental stages. These results suggest that TLR expression in the guinea pig lung is developmentally regulated, enhancing the understanding of lung biology in guinea pig models.

Expression of Toll-Like Receptors in the Lung Tissue of Mouse Fetuses Generated by in vitro Embryo Culture and Embryo Transfer

“…Details surrounding the role of TLRs in fetal development still remain elusive. There is accumulating evidence suggesting that, apart from their function in the establishment of the innate immune response, TLRs might have non-immune functions in various developmental processes including the preservation of tissue architecture [Willet et al, 2000], neurite development [Ma et al, 2017], axonal growth [Cameron et al, 2007], neurogenesis [Barak et al, 2014], and cell proliferation [Lathia et al, 2008;Okun et al, 2010;Ding et al, 2017]. The present study does not provide any functional data.…”

“…The data demonstrating that all functional TLRs are expressed in the lung tissue both at the transcriptional and translational levels and that stress imposed on embryos at preimplantation stages of development is associated with downregulation of TLRs along with some of the genes involved in TLR signaling pathway during the perinatal period are the two major findings of the present study. To date, the expression of a select group of TLRs was examined in the adult [Harju et al, 2001;Harju et al, 2005;Droemann et al, 2003;Sha et al, 2004;Wassef et al, 2004;Hauber et al, 2005;Janardhan et al, 2006;Singh Suri et al, 2006;Schneberger et al, 2009;Schneberger et al, 2013;Juarez et al, 2010;Go et al, 2014;Ma et al, A similar pattern of immunopositivity also appears on the vascular wall (b, d) and at the periphery the terminal saccules (c). In the experimental group, immune-positive cells were observed at the periphery of bronchial/bronchiolar epithelium (e) and epithelial tubes forming the glandular structures (arrows, e, f).…”

“…2017; Wang et al, 2017;Cao et al, 2018;Chen et al, 2019], neonatal [Harju et al, 2001;Harju et al, 2005;Awasthi et al, 2008;Ma et al, 2017], and fetal [Harju et al, 2001;Harju et al, 2005;Prince et al, 2004;Hillman et al, 2008;Salminen et al, 2008;Petrikin et al, 2010] lung tissue. Various TLRs are expressed on both resident cells of the lung as well as infiltrating cells of myeloid and lymphoid origin including bronchial epithelial cells [ Armstrong et al, 2004;Janardhan et al, 2006;Schneberger et al, 2009;Schneberger et al, 2013;Go et al, 2014;Sha et al, 2004], alveolar type II epithelial cells [Droemann et al, 2003;Go et al, 2014], alveolar septal cells [Janardhan et al, 2006;Schneberger et al, 2013], alveolar/ interstitial macrophages [Droemann et al, 2003;Wassef et al, 2004;Maris et al, 2006;Singh Suri et al, 2006;Hoppstädter et al, 2010;Juarez et al, 2010;Schneberger et al, 2013;Go et al, 2014], endothelial cells [Andonegui et al, 2003;Wassef et al, 2004;Janardhan et al, 2006;Singh Suri et al, 2006;Schneberger et al, 2009;Schnberger et al, 2013], and plasmacytoid dendritic cells…”

Targeting the Toll-like receptor pathway as a therapeutic strategy for neonatal infection

“…In neonatal guinea pigs, mRNA expression levels of TLR2, 3, 6, 7, 8, 9, and 10 were significantly increased in the lungs at 45 days of gestation, whereas TLR1 and TLR4 were significantly increased at 52 days suggesting a dynamic and developmental pattern of expression between members of the TLR family. In the guinea pig, all TLRs had significantly higher expression in lung during later gestational age compared with postnatal expression (186). A report by Awasthi et al (187) performed in premature baboons shows that TLR2 and TLR4 gene expression in lung tissue was developmentally regulated.…”