Inflammatory Response to Malaria Infection Sabotages Immune System Protection

    Malaria parasites cause an inflammatory reaction that sabotages our body’s ability to protect itself against the deadly disease, scientists have found for the first time.

    The finding opens up the possibility of improving malaria vaccines by boosting key immune cells needed for long-lasting immunity. This could even include vaccines that have previously been ineffective in clinical trials.

    Researchers found that the same inflammatory molecules that drive the immune response in clinical and severe malaria also prevent the body from developing protective antibodies against the parasite.

      “With many infections, a single exposure to the pathogen is enough to induce production of antibodies that will protect you for the rest of your life,” explains co-senior author Diana Hansen, Ph.D., laboratory head in the division of infection and immunity at the Walter and Eliza Hall Institute of Medical Research (WEHI). “However with malaria it can take up to 20 years for someone to build up sufficient immunity to be protected. During that time, people exposed to malaria are susceptible to reinfection and become sick many times, as well as spreading the disease.”

    Now, Dr. Hansen and her colleagues at WEHI have revealed how the malaria parasite causes an inflammatory reaction that sabotages the body’s ability to protect itself against the infection. The investigators are hopeful that their findings will lead to novel vaccine possibilities or boost existing therapies by enhancing critical immune cells required for lasting immunity.

    The findings from this study were published recently in Cell Reports through an article entitled “Severe Malaria Infections Impair Germinal Center Responses by Inhibiting T Follicular Helper Cell Differentiation.”

    Interestingly, the WEHI researchers found that the same inflammatory molecules that drive the immune response in clinical and severe malaria also prevent the body from developing protective antibodies against the parasite. The scientists note that this isthe first time it had been explicitly shown why the immune system fails to develop immunity during malaria infections.

    Traditionally, malaria infections have been notoriously difficult to manage because the body is awful at developing long-lasting immunity to the parasite—a scenario that has hindered vaccine development for decades.

    “This was complicated by the fact that we didn’t know whether it was the malaria parasite itself or the inflammatory reaction to malaria that was actually inhibiting the ability to develop protective immunity,” Dr. Hansen notes. “We have now shown that it was a double-edged sword: The strong inflammatory reaction that accompanies and, in fact, drives severe clinical malaria is also responsible for silencing the key immune cells needed for long-term protection against the parasite.”

    The WEHI researchers discovered that inflammatory molecules that were being released in response to the parasitic infection were preventing the immune system from developing protective antibodies.

    “Long-term immunity to malaria and other pathogens requires antibody responses,” states co-senior author Axel Kallies, Ph.D., laboratory head in the division of infection and immunity at WEHI. “Specialized immune cells called helper T cells join forces with B cells to generate these protective antibodies. However, we showed that during malaria infection critical inflammatory molecules actually arrest the development of helper T cells and, therefore, the B cells don’t get the necessary instructions to make antibodies.”

      The researchers are excited by their findings and believe that their results could lead to newer, more efficient therapeutics to help control malaria infections, especially in the area of vaccine development.

    “This research opens the door to therapeutic approaches to accelerate development of protective immunity to malaria and improve the efficacy of malaria vaccines,” Dr. Hansen says. “Until now, malaria vaccines have had disappointing results. We can now see a way of improving these responses, by tailoring or augmenting the vaccine to boost development of helper T cells that will enable the body to make protective antibodies that target the malaria parasites.”