West Nile Virus (WNV) is particularly dangerous for the elderly, who constitute a large number of the serious cases and deaths associated with the disease. Though many infected with the virus show no symptoms, things can turn deadly when the virus crosses the blood-brain barrier and attacks the nervous system. The reason that older people are more likely to suffer from severe consequences of WNV may lie in the impairment of critical parts of the early immune response to the virus.

Using mice, researchers from Washington University in Saint Louis analyzed the immune response to WNV infection in young and old mice. They found that 18-month-old mice (the equivalent of elderly humans) were three times more likely to die after WNV infection than 4-month-old (the equivalent of a human young adult) mice were. Scientists measured the amount of virus in various tissues of the mice and found that the older mice had 20 times higher levels of WNV in their brains, which likely caused their deaths.

When a person is exposed to WNV because a mosquito, the early adaptive immune response is believed to be dominated by antibodies. This was supported by the fact that the older mice had a less potent WNV-specific immune response during the earliest phase of the infection, and weaker long-term antibody memory.

Antibody responses are supposed to begin in the lymph nodes close to the initial site of infection (the draining lymph nodes, or DLNs). Following this, helper T and B cells, two vital immune cells, migrate to and interact to form what is called a “germinal center” and produce a specific antibody response to combat the WNV. Researchers found that in the older mice, the formation of such a center was delayed, going along with the weak early antibody response.

Looking at the DLNs more closely, the study showed that the number of helper T cells was reduced, suggesting the immune systems of older mice have trouble getting the cells they need to the lymph nodes. The environment of the DLNs also contained lower levels of immune stimulators called chemokines, which made them less capable of attracting the immune cells necessary for germinal center formation.

Each observed difference between the young and old mice may seem modest, but these small delays are capable of compounding into a larger problem. Even a short delay in immune response can cause a substantially higher early viral load, which subsequently increases the chances that the virus may reach the brain.

The study’s authors write that the research “identifies a series of key early defects associated with immune responses in old animals.” In reference to how this occurred, they say “the delayed antibody and germinal center cell responses are due to trafficking defects, which are compounded by lower levels of chemokines in the lymph node after infection. Ultimately, this leads to blunted adaptive immune responses, higher viral titers, and increased death after West Nile virus infection.”

Source: Diamond M, Richner J, Gmyrek G, Govero J, Tu Y, van der Windt G, et al. Age-Dependent Call Trafficking Defects in Draining Lymph Nodes Impair Adaptive Immunity and Control of West Nile Virus Infection. PLOS Pathogens. 2015.