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Published on: May 7, 2012
Rotavirus activates dendritic cells derived from umbilical cord blood monocytes
D Rosales-Martinez1, L Gutierrez-Xicotencatl2, O Badillo-Godinez3
1Laboratorio de Inmunología Viral, Facultad de Medicina, UAEM, Cuernavaca, Morelos, Mexico; Facultad de Ciencias, UNAM, Mexico, D.F, Mexico.
Insights
Neonatal dendritic cells (DCs) activate in response to rotavirus, similar to adult DCs. However, neonatal DCs exhibit a regulatory profile, producing more IL-10 and TGF-β, unlike the pro-inflammatory adult DCs.
Area of Science:
- Immunology
- Virology
- Neonatal Immunity
Background:
- Rotavirus is a leading cause of infant diarrhea, but immune responses are mainly studied in adults.
- Dendritic cells (DCs) are key immune cells, and their neonatal response to rotavirus is understudied.
- Understanding neonatal DC responses is crucial for infant immunity and vaccine development.
Purpose of the Study:
- To investigate the in vitro response of neonatal and adult dendritic cells (DCs) to rotavirus.
- To compare the activation, cytokine production, and T cell-inducing capabilities of neonatal versus adult DCs upon rotavirus exposure.
Main Methods:
- Monocyte-derived DCs were isolated from umbilical cord blood (neonatal) and adult peripheral blood.
- DCs were stimulated with rotavirus and its genome (dsRNA) in vitro.
- Immune responses were assessed by measuring cell surface markers (CD40, CD86, MHC II, TLR-3, TLR-4), cytokine production (IL-6, IL-12/23p40, IL-10, TGF-β, TNF-α, IFN-β), and T cell proliferation/cytokine production (IFN-γ).
Main Results:
- Rotavirus activated neonatal DCs, up-regulating key immune markers and producing cytokines like IL-6, IL-12/23p40, IL-10, and TGF-β.
- Neonatal DCs supported rotavirus replication and induced robust CD4+ T cell proliferation and IFN-γ production.
- While similar to adult DCs in activation, neonatal DCs displayed a regulatory bias with higher IL-10/TGF-β and less efficient Th1 induction compared to adult DCs.
Conclusions:
- Neonatal DCs are activated by rotavirus and its genome, demonstrating a functional immune response.
- Neonatal DCs possess a distinct tolerogenic bias compared to adult DCs, influencing their immune response profile.
- Rotavirus can infect and replicate within neonatal DCs, highlighting a potential role in infant infection dynamics.
Abstract:
Rotavirus is the most common cause of acute infectious diarrhea in human neonates and infants. However, the studies aimed at dissecting the anti-virus immune response have been mainly performed in adults. Dendritic cells (DCs) play a crucial role in innate and acquired immune responses. Therefore, it is very important to determine the response of neonatal and infant DCs to rotavirus and to compare it to the response of adult DCs. Thus, we determined the response of monocyte-derived DCs from umbilical cord blood (UCB) and adult peripheral blood (PB) to rotavirus in vitro. It was found that the rotavirus and its genome, composed of segmented doubled stranded RNA (dsRNA), induced the activation of neonatal DCs, as these cells up-regulated the levels of CD40, CD86, MHC II, TLR-3 and TLR-4, the production of cytokines IL-6, IL-12/23p40, IL-10, TGF-β (but not of IL-12p70), and the message for TNF-α and IFN-β. This activation enabled the neonatal DCs to induce a strong proliferation of allogeneic CD4+ T cells and the production of IFN-γ. Moreover, neonatal DCs could be infected by rotavirus and sustain its replication. Neonatal DCs had a similar response as adult DCs towards rotavirus and its genome. However, adult DCs had a biased pro-inflammatory response compared to neonatal DCs, which showed a biased regulatory profile, as they produced higher levels of IL-10 and TGF-β, and were less efficient in inducing a Th1 type response. So it can be concluded that rotavirus and its genome can induce the activation of neonatal DCs in spite of their tolerogenic bias.
