Influence of biophysical and biochemical cues on Plasmodium sporozoite dynamics in skin tissue.

BACKGROUND: Malaria infection is initiated when Plasmodium sporozoites are injected by Anopheles mosquitoes into the human skin. These motile parasites must move through the dermal environment to reach blood vessels, and therefore, their ability to sense a broad range of environmental cues is critical for successful infection. The skin is a complex microenvironment with varying extracellular matrix (ECM) composition, stiffness, topography, temperature, and humidity. However, the mechanisms by which sporozoites adapt to and navigate through this landscape remain poorly understood. METHODS: This review briefly summarizes literature on Plasmodium sporozoite motility, with an emphasis on environmental and biochemical cues that influence their behavior. Key studies utilizing intravital imaging; in vitro, in vivo, and ex vivo skin models; and engineered substrates are discussed to explore the role of physical and molecular signals on parasite dynamics. RESULTS: This review shows that sporozoite movement is highly affected by diverse biophysical and biochemical factors, including ECM components, tissue stiffness, and surface topography. However, significant gaps remain in understanding how skin changes, especially those caused by age, inflammation, or mechanical stress, influence sporozoite navigation and successful infection. CONCLUSIONS: It is essential to understand how Plasmodium sporozoites sense and respond to the skin microenvironment for designing targeted interventions. Gaining deeper insight into sporozoite behavior within skin tissue-particularly the underlying signaling pathways and gene expression patterns-combined with advances in diagnostic tools and noninvasive imaging techniques targeting the initial skin-stage infection can facilitate the identification of novel therapeutic targets.