Unexpected Partnership Drives Immunity

Photo: Filters in the body’s drainage system

Two cross sections of a lymph node:
macrophages, which appear as
red in the top image, are sticky
cells that act like flypaper,
trapping viruses and bacteria
when they enter the lymph
node; © HMS

The findings contradict the current view that the production of antibodies, a part of what is called adaptive immunity, are absolutely required to fight off certain types of viral infection.

The immune system has two main branches, innate immunity and adaptive immunity. Innate immunity, which we are born with, is a first line of defence that relies on cells and mechanisms that provide general immune responses. The more sophisticated adaptive immunity, which counts antibody-producing B cells as part of its arsenal, is thought to play a major role in controlling viral infections in mammals. However, adaptive immune responses, each tailored to fend off a particular pathogen, only develop after an initial infection. They also require time to become fully mobilised.

The researchers studied the response of mice to neurotropic vesicular stomatitis virus (VSV), a member of the same family as rabies. VSV can cause flu-like symptoms in humans and is common in livestock and rodents. Mice infected with VSV can suffer fatal invasion of the central nervous system even as they generate a high concentration of anti-VSV antibodies in their system, explains senior study author Ulrich von Andrian.

The research team studied VSV infection in B cell–deficient mice and in transgenic mice that had B cells but did not produce antibodies. Unexpectedly, while the former succumbed to VSV infection, the latter were completely protected. So survival after VSV exposure depends on B cells, but does not require antibodies or other aspects of traditional adaptive immunity.

Much of the work of the immune system takes place in the lymph nodes. There, innate immune cells called subcapsular sinus (SCS) macrophages act as a kind of flypaper, trapping viruses and other potential pathogens as they flow through the lymph. “We discovered an intimate relationship between the SCS macrophages and the B cells that is crucial for generating the rapid first response that prevents a dangerous systemic infection,” said first author Ashley Moseman.

The researchers determined that the B cells produced a protein needed to maintain a unique protective function of SCS macrophages. This crucial signal from the B cells enabled the SCS macrophages to produce type I interferons, which were required to prevent fatal VSV invasion. “It will be important to further dissect the role of antibodies and interferons in immunity against similar viruses that attack the nervous system, such as rabies, West Nile virus, and encephalitis,” von Andrian said.

MEDICA.de; Source: Harvard Medical School (HMS)