10 June 2017
A stroke, caused by constricted blood flow to the brain, severely affects the immune system, which can make patients highly susceptible to potentially fatal infections. The cellular and molecular mechanisms that impair the immune system after a stroke are not yet fully understood.
Connie Wong, Paul Kubes and colleagues at Monash University in Melbourne, Australia and the University of Calgary in Canada have revealed crucial details about how a stroke triggers a large shift in the activity of specialized immune cells called invariant natural killer T-cells (iNKT cells)1.
“It has been proposed that the brain suppresses the immune system after a stroke to protect itself from overwhelming inflammation,” says Wong. “But a side-effect of activating anti-inflammatory pathways is an increased susceptibility to infection.”
In previous work on animals2, the team showed that iNKT cells played a key role in regulating the host response to infection after stroke. To investigate whether the function of iNKT cells was also affected in humans after strokes, the researchers collected blood from 36 patients on several occasions after they were admitted to hospital, and screened for infections such as pneumonia, cellulitis and urinary tract infection.
The blood results showed that iNKT cells were three times more active in stroke patients than in healthy ones. This was associated with an increased production of an anti-inflammatory cytokine called interleukin-10, suppressing the immune response and rendering the host more vulnerable to bacterial infections. This shift in immunity was seen in iNKTs in the blood and in the liver, and often persisted three months after the initial stroke.
The findings fit the general emerging theory that brain damage after a stroke is not only linked to cerebral processes, but mediated by the wider immune system. Moreover, therapies that target iNKT cells could present promising alternatives to antibiotics for tackling post-stroke infections, especially given the growing problem of antibiotic resistance in pathogens.
“In the future, we will assess the capacity of novel agents that specifically target and modulate iNKT cells, with the aim of reversing immune deficits in stroke patients,” says Wong.
Immunomodulation therapies that augment the immune system to combat infections are an attractive avenue, the researchers conclude in their study published in the journal Frontiers in Neurology. However, they warn caution is needed to ensure further cerebral injury is avoided.
- Wong, C. H. Y., Jenne, C. N., Tam, P. P., Léger, C., Venegas, A. et al. Prolonged activation of invariant natural killer T cells and TH2-skewed immunity in stroke patients. Frontiers in Neurology 8 (2017) | article
- Wong, C.H.Y., Jenne, C.N., Lee, W.Y., Léger, C., Kubes, P. Functional innervation of hepatic iNKT cells is immunosuppressive following stroke. Science 334, 101-105 (2011) | article