Abstract
Cholinergic chemosensory cells (CCC) are infrequent epithelial cells with immunosensor function, positioned in mucosal epithelia preferentially near body entry sites in mammals including man. Given their adaptive capacity in response to infection and their role in combatting pathogens, we here addressed the time points of their initial emergence as well as their postnatal development from first exposure to environmental microbiota (i.e., birth) to adulthood in urethra and trachea, utilizing choline acetyltransferase (ChAT)-eGFP reporter mice, mice with genetic deletion of MyD88, toll-like receptor-2 (TLR2), TLR4, TLR2/TLR4, and germ-free mice. Appearance of CCC differs between the investigated organs. CCC of the trachea emerge during embryonic development at E18 and expand further after birth. Urethral CCC show gender diversity and appear first at P6-P10 in male and at P11-P20 in female mice. Urethrae and tracheae of MyD88- and TLR-deficient mice showed significantly fewer CCC in all four investigated deficient strains, with the effect being most prominent in the urethra. In germ-free mice, however, CCC numbers were not reduced, indicating that TLR2/4-MyD88 signaling, but not vita-PAMPs, governs CCC development. Collectively, our data show a marked postnatal expansion of CCC populations with distinct organ-specific features, including the relative impact of TLR2/4-MyD88 signaling. Strong dependency on this pathway (urethra) correlates with absence of CCC at birth and gender-specific initial development and expansion dynamics, whereas moderate dependency (trachea) coincides with presence of first CCC at E18 and sex-independent further development.
Highlights
Referring to their apical brush or tuft of stiff microvilli, identified in ultrastructural studies, a group of rare solitary epithelial cells has been initially termed brush or tuft cells (Rhodin and Dalhamn 1956; Sbarbati and Osculati 2005)
The time course of urethral Cholinergic chemosensory cells (CCC) appearance showed a sexual dimorphism in choline acetyltransferase (ChAT)-eGFP mice (Fig. 1)
The present data indicate at least a modulating and enhancing influence of the developing microbiota on the postnatal population dynamics of CCC, albeit microbiota are not an absolute requirement for the occurrence of CCC
Summary
Referring to their apical brush or tuft of stiff microvilli, identified in ultrastructural studies, a group of rare solitary epithelial cells has been initially termed brush or tuft cells (Rhodin and Dalhamn 1956; Sbarbati and Osculati 2005). Cell and Tissue Research (2021) 385:21–35 chemosensory cells (CCC) have been identified in the upper airways (Saunders et al 2014; Tizzano et al 2011), the vomeronasal organ (Ogura et al 2010), the auditory tube (Krasteva et al 2012b), the trachea (Krasteva et al 2011), the conjunctiva (Wiederhold et al 2015), the gastro-intestinal tract including the gall bladder (Schutz et al 2015), the urethra (Deckmann et al 2014), and the thymus (Panneck et al 2014) All cells of this category are closely related, even though there are organ-specific characteristics (Deckmann and Kummer 2016; Finger and Kinnamon 2011; Nadjsombati et al 2018; O’Leary et al 2019). They have been attributed with a sentinel function and are regarded as crucial elements of the mucosal innate immune system (Krasteva and Kummer 2012; Kummer and Deckmann 2017; Middelhoff et al 2017; Schneider et al 2019; Tizzano and Finger 2013)
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