Intestinal CD103+ Dendritic Cells Are Key Players in the Innate Immune Control of Cryptosporidium parvum Infection in Neonatal Mice

Abstract

Cryptosporidium parvum is a zoonotic protozoan parasite found worldwide, that develops only in the gastrointestinal epithelium and causes profuse diarrhea. Using a mouse model of C. parvum infection, we demonstrated by conditional depletion of CD11c+ cells that these cells are essential for the control of the infection both in neonates and adults. Neonates are highly susceptible to C. parvum but the infection is self-limited, whereas adults are resistant unless immunocompromised. We investigated the contribution of DC to the age-dependent susceptibility to infection. We found that neonates presented a marked deficit in intestinal CD103+ DC during the first weeks of life, before weaning, due to weak production of chemokines by neonatal intestinal epithelial cells (IEC). Increasing the number of intestinal CD103+ DC in neonates by administering FLT3-L significantly reduced susceptibility to the infection. During infections in neonates, the clearance of the parasite was preceded by a rapid recruitment of CD103+ DC mediated by CXCR3-binding chemokines produced by IEC in response to IFNγ. In addition to this key role in CD103+ DC recruitment, IFNγ is known to inhibit intracellular parasite development. We demonstrated that during neonatal infection CD103+ DC produce IL-12 and IFNγ in the lamina propria and the draining lymph nodes. Thus, CD103+DC are key players in the innate immune control of C. parvum infection in the intestinal epithelium. The relative paucity of CD103+ DC in the neonatal intestine contributes to the high susceptibility to intestinal infection.

Interleukin-12-Producing CD103+CD11b−CD8+Dendritic Cells Are Responsible for Eliciting Gut Intraepithelial Lymphocyte Response against Encephalitozoon cuniculi

“…But as shown in the current report, ϩ DC loaded with OVA can exhibit a classical DC function and initiate a significant immune response in the MLN (37). The importance of CD103 ϩ DC in the mucosal immune response against an oral pathogen is further emphasized by a very recent study using a neonate model of C. parvum infection (50). In agreement with these observations, we demonstrate in this study that LP CD103 ϩ CD11b Ϫ CD8 ϩ DC are able to traffic to the MLN and that S1P blockade inhibits this process.…”

CpG Oligodeoxynucleotides Facilitate Delivery of Whole Inactivated H9N2 Influenza Virus via Transepithelial Dendrites of Dendritic Cells in Nasal Mucosa

“…ϩ DCs rather than CD103 ϩ DCs have been consistently observed to sample the intestinal luminal content by extending TEDs (56)(57)(58). Recently, CD103…”

“…ϩ DCs have been shown to be capable of efficiently sampling luminal bacteria by using their intraepithelial dendrites and then migrating into the mesenteric lymph nodes (57,59). In the lung, CD103…”

The gut flora is required for the control of intestinal infection by poly(I:C) administration in neonates

“…The age-dependent susceptibility to this intestinal infection is associated with incomplete colonization of the lamina propria by various types of immune cells, including dendritic cells (DCs), macrophages and T lymphocytes, and low basal levels of the type II interferon required to prevent parasite development in epithelial cells. 3- 5 We recently highlighted the importance of innate immunity for control of the acute phase of this infection in neonatal mice, with intestinal DCs, which are massively recruited during infection, playing a particularly crucial role. 5 During infection, immune responses are generally triggered by the recognition of microbial molecules by cellular sensors known as pattern recognition receptors (PRR), such as Toll-like receptors (TLRs), Nod-like receptors (NLRs) and helicases.…”

“…3- 5 We recently highlighted the importance of innate immunity for control of the acute phase of this infection in neonatal mice, with intestinal DCs, which are massively recruited during infection, playing a particularly crucial role. 5 During infection, immune responses are generally triggered by the recognition of microbial molecules by cellular sensors known as pattern recognition receptors (PRR), such as Toll-like receptors (TLRs), Nod-like receptors (NLRs) and helicases. In the intestine, these innate receptors are expressed on intestinal epithelial cells and on immune cells, such as mononuclear phagocytes.…”