Influenza A Virus Impairs Control of Mycobacterium tuberculosis Coinfection Through a Type I Interferon Receptor–Dependent Pathway

Abstract

Influenza followed by severe acute bacterial pneumonia is a major cause of mortality worldwide. Several mechanisms account for this enhanced susceptibility, including increased production of type I interferon (IFN). In individuals infected with Mycobacterium tuberculosis, the influence of acute viral infections on tuberculosis progression is unclear. We show that prior exposure of mice to influenza A virus, followed by M. tuberculosis infection, leads to enhanced mycobacterial growth and decreased survival. Following M. tuberculosis/influenza virus coinfection, mycobacterial growth is enhanced by a type I IFN signaling pathway. Our findings highlight the detrimental influence influenza virus infection can have before or during M. tuberculosis infection.

Host-directed therapy of tuberculosis based on interleukin-1 and type I interferon crosstalk

“…This leads to excessive type I IFN expression that in turn causes increased bacterial replication and pathology, thus modelling the type I IFN-associated uncontrolled active disease that occurs in a subset of TB patients 20–22 . c , Likewise, experimental induction of type I IFNs by pICLC or viral co-infections 33 creates a detrimental environment with uncontrolled bacterial growth and extracellular bacteria, ultimately resulting in loss of host resistance and increased mortality. d , HDT targeting PGE2, either directly or indirectly by enhancing PGE2 levels via 5-LO inhibition with zileuton, returns the system to a non-pathological steady state by limiting type I IFN-driven disease exacerbation, bacterial replication and pulmonary necrosis.…”

Guarding the frontiers: the biology of type III interferons

“…The difference between the effects of type I and type III IFNs might be important especially in the context of viral-bacterial coinfection, which is seen frequently during influenza virus infections, for example, and can lead to severe disease 84,85 . Therefore, type III IFN is keeping the borders clear of viral infection without causing widespread immune activation, but it could also be better than type I IFN in steering clear of interfering with the antibacterial immune responses required during polymicrobial exposure.…”

Tuberculosis Comorbidity with Communicable and Noncommunicable Diseases

“…Mouse models have shown that prior exposure to influenza A impairs immune responses to Mtb infection and decreases survival (Redford et al 2014), possibly through down-regulated MHC (major histocompatibility complex) expression on dendritic cells and reduced activation of CD4 and CD8 T cells to clear mycobacteria (Florido et al 2013). A similar murine study found influenza had little effect on mycobacterial load (Co et al 2006).…”