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cDC1 deficient mice are protected from reinfection with rotavirus despite a reduced neonatal plasma cell response

van Dijl, Sharné (2020) BIOY01 20202
Degree Projects in Biology
Popular Abstract
Rotavirus and the Neonate: Memories of infections gone by

Despite advances made through vaccination, the disease burden of rotavirus in the developing world remains high, largely affecting children below the age of 5 and remaining the leading cause of death from viral gastroenteritis (Fig. 1). Socio-economic factors, as well as poor response to vaccination in the developing world are believed to be responsible for the stark contrast with the developed world. As childhood marks a period of increased risk for infections such as rotavirus, attempts have been made to vaccinate children from birth. Due to the immaturity of their immune system, vaccination of young children poses a challenge. This highlights the need for a deeper... (More)
Rotavirus and the Neonate: Memories of infections gone by

Despite advances made through vaccination, the disease burden of rotavirus in the developing world remains high, largely affecting children below the age of 5 and remaining the leading cause of death from viral gastroenteritis (Fig. 1). Socio-economic factors, as well as poor response to vaccination in the developing world are believed to be responsible for the stark contrast with the developed world. As childhood marks a period of increased risk for infections such as rotavirus, attempts have been made to vaccinate children from birth. Due to the immaturity of their immune system, vaccination of young children poses a challenge. This highlights the need for a deeper understanding of immune development and the mechanisms involved in protection against infection in young children.

In adults, the immune response to rotavirus is driven by a range of immune cells, with antibodies providing protection from reinfection. The first line of contact with the immune response, however, is provided through cells known as dendritic cells. These cells are crucial inducers of effector immune cells, such as antibody producing cells and cells killing infected cells, and are therefore attractive targets for vaccine strategies. Based on several properties, these cells can be divided into several subsets, each playing a specific role in the immune system. Of importance in rotavirus infection is a population known as ‘conventional dendritic cells’ (cDC), which can be further divided into two subsets known as cDC1 and cDC2. By using genetically modified mice infected with rotavirus, human rotavirus infection can be modelled, allowing us to study the immune response to this virus. Adult mice lacking the cDC1 have been shown to have an impaired immune response to rotavirus. In these mice, our laboratory has shown that the absence of cDC1 results in a reduction in antibody producing cells known as ‘plasmablasts’. Due to the differences between the adult and young immune system, we aimed to investigate what effect the absence of cDC1 has on the neonatal rotavirus response, focusing on these antibody producing plasmablast cells. Neonatal mice showed a significant reduction in plasmablast cells (Fig. 2), but in contrast to adults, no significant reduction in the protective antibodies. This indicates alternate mechanisms functioning in the neonatal antibody response to rotavirus. In addition, we demonstrated that despite this altered antibody response in mice lacking cDC1s, mice infected as pups could not be reinfected as adults. The mechanisms involved in the induction of antibody-producing cells in neonates remains a point of interest in our laboratory for future study.

Handledare: Katharina Lahl, Konjit Getachew
Examensarbete 30hp i BIOY01, 2020
Biologiska institutionen, Lunds universitet (Less)
Please use this url to cite or link to this publication:
author
van Dijl, Sharné
supervisor
organization
course
BIOY01 20202
year
type
M2 - Bachelor Degree
subject
language
English
id
9031769
date added to LUP
2020-11-10 09:58:29
date last changed
2020-11-10 09:58:29
@misc{9031769,
  author       = {{van Dijl, Sharné}},
  language     = {{eng}},
  note         = {{Student Paper}},
  title        = {{cDC1 deficient mice are protected from reinfection with rotavirus despite a reduced neonatal plasma cell response}},
  year         = {{2020}},
}