Researchers Discover Protein That Facilitates Immunity Against Malaria

In 2015, malaria claimed the lives of more than 400,000 people, primarily in developing countries, according to the World Health Organization (WHO).

Although the incidence of the mosquito-borne virus has declined since the beginning of the 21^st century—from 262 million cases in 2000 to 214 million last year, based on WHO estimates—it remains a stubborn public health challenge, due primarily to what public health officials say is the failure of current antimalarial drugs to offer 100% protection against the disease.

However, a discovery by researchers at Houston Methodist, a hospital system that includes academic and research centers in addition to medical facilities, has generated a significant amount of optimism in efforts to eradicate malaria. In a study published in the November 15 issue of the journal Immunity, scientists at the Texas institution describe the discovery of a protein that facilitates immunity against the virus.

According to the study’s lead author, Rongfu Wang, PhD, director, Center for Inflammation and Epigenetics at Houston Methodist, in comments exclusive to Contagion, the findings will help future researchers seeking to develop vaccines against malaria, “understand the whole picture of how innate immune signaling and regulation dictate immunity against different malaria strains for more broad malaria vaccines.”

Indeed, Dr. Wang and his colleagues believe that their discovery, which was made during experiments with mouse models infected with malaria, will ultimately provide researchers with the potential to develop a vaccine against the mosquito-borne virus and other diseases, even cancer. It has been known for some time that type I interferon “is critical for controlling pathogen infection,” the authors noted in the Immunity paper. However, precisely how the protein is regulated in the immune system currently remains largely unknown.

Dr. Wang and his team discovered that (nucleic acid sensors) cGAS-, STING-, MDA5-, MAVS-, or transcription factor IRF3-deficient mice produced high amounts of type I interferon-alpha and interferon-beta, and thus, were resistant to malaria infection (yoelii YM). They also noted that this high production of type 1 interferon ceased when “gene encoding nucleic acid sensor TLR7, signaling adaptor MyD88, or transcription factor IRF7 was ablated or [plasmacytoid dendritic cells] were depleted” in the experimental mice. Additional experiments identified SOCS1 as “a key negative regulator” that inhibits MyD88-dependent type I interferon signaling in plasmacytoid dendritic cells, and demonstrated that plasmacytoid dendritic cells, conventional dendritic cells, and macrophages were necessary to produce the protective immunity afforded by type 1 interferon-alpha and —beta proteins.

Dr. Wang and his team are now working with “different lethal strains [of malaria] due to their strain-specific innate immune response” to see if they can replicate their findings. In Immunity, they wrote, “[O]ur findings have identified a critical regulatory mechanism of type I interferon signaling in [plasmacytoid dendritic cells] and stage-specific function of immune cells in generating potent immunity against lethal YM [malaria] infection.”

Brian P. Dunleavy is a medical writer and editor based in New York. His work has appeared in numerous healthcare-related publications. He is the former editor of Infectious Disease Special Edition.