Towards a Molecular Understanding of Host Specificity in Hookworm Infections
Open Access DepositedHookworm infects millions globally, resulting in chronic health issues such as malnutrition and anemia. The difficulties managing these infections are complicated by the absence of effective vaccines and the emergence of resistance to anthelmintics in livestock and companion animals, a potential risk in human treatments. Understanding the molecular interplay between parasites and their hosts is essential for unraveling the complexities of infection, including establishment, parasite development, larval expulsion and/or larval tissue arrest. When parasites encounter a host-specific chemical signature, it signals arrival in a favorable environment. This encounter initiates a cascade of molecular events initiating parasite development in the host, yet these events remain largely unidentified for most parasitic species. By utilizing hookworms from the genus Ancylostoma, known for their pronounced host specificity, this dissertation sought to dissect the molecular crosstalk between hookworms and their hosts that determine whether the parasite can successfully colonize the host. These findings could potentially inform new treatment strategies against hookworm infections and deepen our understanding of parasite biology. The chemosensory mechanisms of hookworms essential for locating hosts and initiating infection are detailed in Chapters 1 and 2. In Chapters 3 and 4, the focus shifts to the host side of the host-parasite relationship, revealing a complex immune landscape that differs in non-permissive and permissive hosts that hookworms must navigate to establish infection. Finally, Chapter 5 delves into the host immune response and investigates various other host components that hookworms may exploit either to initiate or to inhibit development, also highlighting a sex-specific pathway involved in protecting against hookworm infection. Overall, the research presented herein advances our understanding of the complex interactions between hookworms and their hosts and suggests new directions for future investigation.
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Langeland_gwu_0075A_16753.pdf | 2024-10-02 | Open Access |
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