Abstract
Paneth cells are major secretory cells located in the crypts of Lieberkühn in the small intestine. Our understanding of the diverse roles that Paneth cells play in homeostasis and disease has grown substantially since their discovery over a hundred years ago. Classically, Paneth cells have been characterized as a significant source of antimicrobial peptides and proteins important in host defense and shaping the composition of the commensal microbiota. More recently, Paneth cells have been shown to supply key developmental and homeostatic signals to intestinal stem cells in the crypt base. Paneth cell dysfunction leading to dysbiosis and a compromised epithelial barrier have been implicated in the etiology of Crohn’s disease and susceptibility to enteric bacterial infection. Our understanding of the impact of Paneth cells on viral infection is incomplete. Enteric α-defensins, produced by Paneth cells, can directly alter viral infection. In addition, α-defensins and other antimicrobial Paneth cell products may modulate viral infection indirectly by impacting the microbiome. Here, we discuss recent insights into Paneth cell biology, models to study their function, and the impact, both direct and indirect, of Paneth cells on enteric viral infection.
Highlights
Paneth cells are major secretory cells located in the crypts of Lieberkühn in the small intestine
Like mouse adenovirus 2 (MAdV-2) resistance to mouse enteric α-defensins, human defensin 5 (HD5) resistance of fecal/orally transmitted human adenovirus (HAdV) may reflect viral evolution. Another case in which barrier integrity mediated by Paneth cells is compromised by viral infection occurs in intestinal dysbiosis following human immunodeficiency virus (HIV) infection
Paneth cells play an integral part in stem cell maintenance, microbiome shaping, and host defense
Summary
Paneth cells are located at the base of the crypts of Lieberkühn in the small intestine of various animals and are interspersed amongst the intestinal stem cells from which they differentiate [1,2,3,4,5,6,7,8]. A naturally occurring peptide derived from this protein has anti-HIV activity [39] Of these antimicrobial peptides and proteins, Paneth cells are the sole epithelial source within the intestine of α-defensins [40], lysozyme [41], sPLA2 [42], and Ang4 [20], while RegIIIγ, RegIIIβ, and α1-antitrypsin are produced by other epithelial cell types [43,44]. Wnt signaling controls the expression of some Paneth cell-specific secretion products (e.g., MMP7, enteric α-defensins), transcription factors required for Paneth cell differentiation (SOX9), and signaling molecules that dictate proper positioning along the crypt/villus axis (EphB2 and EphB3) (see Section 6 below) [58]. Activation of the Notch pathway results in increased proliferation in the stem cell compartment with a concomitant loss in secretory cell differentiation [60]
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