Highly Pathogenic Influenza Virus Infection of the Thymus Interferes with T Lymphocyte Development

Abstract

Highly pathogenic avian influenza viruses (HPAIVs) cause severe disease in humans. Still, the basis for their increased pathogenesis remains unclear. Additionally, the high morbidity in the younger population stays inexplicable, and the recent pandemic H1N1v outbreak in 2009 demonstrated the urgent need for a better understanding about influenza virus infection. In the present study, we demonstrated that HPAIV infection of mice not only led to lung destruction but also to functional damage of the thymus. Moreover, respiratory dendritic cells in the lung functioned as targets for HPAIV infection being able to transport infectious virus from the lung into the thymus. The pandemic H1N1 influenza virus was able to infect respiratory dendritic cells without a proper transport to the thymus. The strong interference of HPAIV with the immune system is especially devastating for the host and can lead to lymphopenia. In summary, from our data, we conclude that highly pathogenic influenza viruses are able to reach the thymus via dendritic cells and to interfere with T lymphocyte development. Moreover, this exceptional mechanism might not only be found in influenza virus infection, but also might be the reason for the increased immune evasion of some new emerging pathogens.

NK-cells are involved in thymic atrophy induced by influenza A virus infection

“…Apoptosis of thymic T-cells (especially DP T-cells) has been reported to be the main cause of thymic atrophy (Liu et al, 2014;Savino, 2006;Vogel et al, 2010). In our study, in addition to DP T-cell apoptosis we found that influenza virus infection significantly suppressed the proliferation of thymic T-cells (especially DN T-cells), as shown by the obvious decrease in BrdU incorporation (Fig.…”

“…This discrepancy might be caused by differences in the infecting virus dose, virulence and mouse strains. Vogel et al (2010) showed that highly pathogenic IAV could infect the thymus and interfere with T-cell development. Liu et al (2014) showed that elevated IFN-c produced by innate CD8…”

“…Trypanosoma cruzi, Plasmodium chaubi) and fungal infections (exemplified by experimental infections with Paracoccidioides brasiliensis and Histoplasma capsulatum) (Savino, 2006). To date, several mechanisms have been implicated in influenza virus infection-induced thymic atrophy, such as interference with T-lymphocyte development, increased levels of glucocorticoids and elevated IFN-c production by innate CD8 + T-cells (Liu et al, 2014;Tian et al, 2012;Vogel et al, 2010).…”

Lymphopenia Associated with Highly Virulent H5N1 Virus Infection Due to Plasmacytoid Dendritic Cell–Mediated Apoptosis of T Cells

“…Lymphopenia can result from impaired development or destruction of lymphocytes. Vogel et al reported that H5N1 virus infection in mice led to massive lung damage and infection of respiratory DCs, and proposed that the migration of infected DCs into the thymus interferes with T lymphocyte selection processes (29). We show that lethal highly pathogenic avian influenza (HPAI) H5N1 influenza virus infection results in increased destruction of lymphocytes by up-regulation of FasL expression on pDCs and that FasL+ pDCs are responsible for apoptosis of influenza-specific CD8 + T cells.…”

Comment on “Highly Pathogenic Influenza Virus Infection of the Thymus Interferes with T Lymphocyte Development”

“…Comment on "Highly Pathogenic Influenza Virus Infection of the Thymus Interferes with T Lymphocyte Development" I read with much interest the article by Vogel et al (1), who state that the cause for lymphopenia in severe infections has been hitherto unclear and, based on their findings, propose that highly pathogenic infectious agents such as influenza virus directly impede the development of lymphocytes, and hence account for lymphopenia. However, the authors have overlooked a well-studied and very important mechanism for lymphopenia, one involving glucocorticoids, which have been used as chemotherapeutic agents against hematological malignancies for decades.…”