Abstract
Viral and bacterial infections of the lower respiratory tract are major causes of morbidity and mortality worldwide. Alveolar macrophages line the alveolar spaces and are the first cells of the immune system to respond to invading pathogens. To determine the similarities and differences between the responses of mice and macaques to invading pathogens we profiled alveolar macrophages from these species following infection with two viral (PR8 and Fuj/02 influenza A) and two bacterial (Mycobacterium tuberculosis and Francisella tularensis Schu S4) pathogens. Cells were collected at 6 time points following each infection and expression profiles were compared across and between species. Our analyses identified a core set of genes, activated in both species and across all pathogens that were predominantly part of the interferon response pathway. In addition, we identified similarities across species in the way innate immune cells respond to lethal versus non-lethal pathogens. On the other hand we also found several species and pathogen specific response patterns. These results provide new insights into mechanisms by which the innate immune system responds to, and interacts with, invading pathogens.
Highlights
Lower respiratory tract infections are the single largest cause of death in low income countries and the fourth largest cause of death in middle and high income countries [1,2]
Our study examines the ability of alveolar macrophages (AM) obtained from mice and macaques to respond to the same pathogens
We examined responses, using Luminex and microarrays, to the bacteria Mycobacterium tuberculosis (Mtb) and Francisella tularensis (Ft) subspecies tularensis, strain Schu S4. (Schu S4) and two influenza A viruses, A/Fujian/411/2002(H3N2) (Fuj/02) and the mouse adapted A/PR8/34(H1N1) (PR8)
Summary
Lower respiratory tract infections are the single largest cause of death in low income countries and the fourth largest cause of death in middle and high income countries [1,2]. The infections may be caused by bacteria (e.g., Mycobacterium tuberculosis) or viruses (e.g., influenza). Influenza virus infects 5–10% of the world’s population each year and results in approximately 500,000 deaths annually [3]. A third of the world’s population is thought to be infected with Mycobacterium tuberculosis (Mtb) [2]. While therapies and vaccines exist for many of these infections there is a need to increase our understanding of the early host response to these infections. When new influenza viruses appear each year due to antigenic variation, the early immune response can either be excessive leading to increased morbidity and mortality, or be inadequate thereby allowing the pathogen to spread beyond the confines of the lung [5]. Comparing and contrasting the early host responses to diverse pathogens will provide valuable insight into the pathogenesis of emerging and biodefense pathogens
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