Immune tolerance and human malaria

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Background

Exposure to malaria parasites induces immune modulations that affect susceptibility to malaria as well as other pathogens. Development of immunity to malaria results in protection against severe disease, though sterile immunity is typically not achieved and adults living in endemic areas frequently carry parasites without symptoms. This ‘clinical immunity’ comprises both anti-parasite mechanisms that mediate parasite clearance and immunoregulatory mechanisms that limit immunopathology (tolerance). The mechanisms underlying tolerance to blood-stage infection are not well defined. Recent studies highlight the importance of immunoregulatory functions of cells such as monocytes, γδ T cells, and IL-10-producing T cells in limiting immunopathology, though additional mechanistic studies are needed to understand the protective vs. pathogenic role these cells play in malaria. Further defining the role of immune tolerance in host protection against malaria may aid in the development of new therapies and improved vaccines.

Exposure to malaria in utero has immunomodulatory effects that are distinct from those seen in children and older individuals, with significant clinical consequences. Infants born to mothers with pregnancy-associated malaria develop their first malaria infection earlier, have more infections during infancy (due to malaria and other pathogens), and have lower antibody responses to vaccines. Data suggest that in utero exposure to malaria antigens induces an immune tolerant phenotype, yet recent studies also report that in utero exposure is associated with the generation of pro-inflammatory malaria-responsive fetal T and B cells. A better understanding of the consequences of priming the fetal immune system with malarial antigens is critical for the development of vaccines targeting pregnant women and young infants.

With this Research Topic, we aim to provide further insights into the role of malaria-induced immune tolerance in protection against malaria as well as susceptibility to other infectious diseases. Our understanding of the immunological mechanisms that determine protection is challenged by a number of other important factors, and we welcome studies that may also take into account: complexity of the parasite life cycle, differences among Plasmodium species, parasite immune-evading mechanisms, differences in malaria transmission patterns, and prevalence of co-infections. We propose to focus the collection on studies of human malaria, including immuno-epidemiological cohort studies and controlled human malaria infections.

We seek Original Research, Review, Mini Review, Hypothesis and Theory, Perspective, and Opinion articles focusing on, but not strictly limited to, the following topics:
• Effect of in utero malaria exposure (including timing and magnitude of maternal infection) on infant immune ontogeny, risk for malaria and other infections
• Malaria-induced long-term changes in innate immune cells (innate immune memory, trained immunity)
• Malaria-induced immunoregulatory responses of the adaptive immune system
• Immune tolerance mechanisms specific to Plasmodium vivax infection
• Parasite-host interactions that promote disease tolerance
• Immunomodulatory effects of co-infections (such as helminths, EBV, CMV) that influence host protection against malaria
• Malaria-induced immune modulation and susceptibility to other infectious diseases
• Malaria-induced immune modulation and vaccine efficacy in malaria-endemic areas.

Keywords: Immune tolerance, primed immunity, human malaria, malaria in pregnancy, fetal immunity, disease tolerance

Important note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

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