This episode of TWIP (This Week in Parasitism) features a deep dive into two distinct research papers related to parasitology. The first paper, published in Cell, investigates how a commensal gut protozoan, Trichamonas musculus (T-mu), in mice influences distant pulmonary immunity. It details a complex pathway where T-mu, interacting with the bacterial microbiome, stimulates gut-resident ILC2 cells. These ILC2s then traffic to the lung via sphingosine receptors, promoting lung eosinophilia in a process mediated by T and B cells and specific molecules like OX40, IL2, and Icos ligand. The study reveals that this T-mu-induced eosinophilia has contrasting effects: it exacerbates allergic airway inflammation but surprisingly restricts the dissemination of Mycobacterium tuberculosis from the lungs to other organs like the spleen. The second paper, from Scientific Reports, explores the adaptations of ectoparasites, specifically seal lice, to life on pinnipeds that engage in deep diving. It highlights how these lice have co-evolved with their hosts and possess remarkable features allowing them to survive high pressures and aquatic environments. A key finding is that lice from deeper-diving seal species tend to have a rounder body shape, hypothesized as an adaptation to withstand the rapid, intense pressure changes experienced during host dives. The discussion underscores the value of studying diverse parasitic systems and curiosity-driven research.
TWIP 258: The Deeper the Rounder - Summarizing Two Papers
0:24 Paper Day Theme: The episode focuses on research papers, particularly exploring how gut microbes, including parasites, can impact immune responses in distant parts of the body.
04:15 Paper 1: Gut Protozoan Shaping Pulmonary Immunity: The first paper discussed is a Cell study titled "A gut commensal protozoan determines respiratory disease outcomes by shaping pulmonary immunity," which investigates the effects of Trichamonas musculus (T-mu), a protozoan found in mice guts.
06:00 Gut-Lung Axis & ILC2s: The discussion introduces the concept of the gut microbiome influencing health and disease in other organs, like the lungs (the gut-lung axis). Group 2 innate lymphoid cells (ILC2s), known to be involved in asthma and helminth infections, are highlighted as key players that can travel from the gut to the lung.
10:07 T-mu Induces Lung Eosinophilia: T-mu colonization in mice, even though the protozoan stays in the gut, leads to a systemic increase in eosinophils (a type of immune cell), particularly in the lungs. This effect is shown to be caused by increased production of eosinophils in the bone marrow and their subsequent homing to mucosal tissues, including the lung.
16:25 ILC2 Migration Mediated by Sphingosine: Experiments demonstrate that ILC2s from the gut migrate to the lung. This migration is linked to elevated serum levels of sphingosine (a signaling molecule) induced by T-mu, and specifically relies on sphingosine receptors (S1PR4) on the ILC2s. Blocking these receptors prevents ILC2 accumulation in the lung.
20:28 Microbiome & Succinate Involvement: The T-mu's effect on lung eosinophilia requires the presence of the bacterial microbiome. Succinate, a metabolite potentially produced by the microbiome or the parasite, can partially mimic the T-mu effect when given to mice, suggesting it is a key mediator in triggering this immune response.
27:08 Tripartite Immune Interaction: The induction of lung eosinophilia requires a complex interaction between ILC2s, T cells (specifically CD4+ T cells), and B cells, in addition to the presence of T-mu and the bacterial microbiome. Soluble factors like IL2 and OX40, produced by these immune cells, help sustain the ILC2 accumulation.
34:08 Contrasting Effects on Respiratory Disease: While the T-mu induced eosinophilia worsens allergic airway inflammation (an asthma model) in mice, it surprisingly provides a benefit in the context of Mycobacterium tuberculosis (TB) infection.
40:30 Protection Against TB Dissemination: T-mu colonization does not reduce the number of TB bacteria in the lungs but significantly inhibits their dissemination to other organs like the spleen. This protection correlates with the presence of elevated lung eosinophils, and depleting these cells removes this protective effect.
45:18 Disseminated TB: The discussion includes a personal anecdote about disseminated TB, highlighting that TB can spread from the lungs to various organs and reactivate years later, particularly in immunocompromised individuals.
49:04 Clinical Implications: The findings suggest potential re-examination of clinical trials for asthma therapies targeting IL5, OX40L, and sphingosine receptors, considering the possible influence of commensal protozoa. It also raises the possibility of manipulating eosinophils to impact TB dissemination, although the commensal-induced effect is temporary.
50:02 Paper 2: Ectoparasites & Seal Lice: The second paper explores the unique adaptations of seal lice, ectoparasites living on seals and other pinnipeds that perform deep dives.
51:19 Seal Lice Adaptations: Seal lice have co-evolved with their hosts, adapting to marine life and deep diving. They possess strong legs to hold onto hair and closable spiracles (breathing openings) to trap air and prevent water entry during dives.
56:12 The Deeper the Rounder: Morphological analysis shows that seal lice living on hosts that dive deeper tend to have a rounder body shape, hypothesized to be an adaptation to better withstand the rapidly changing, high pressures encountered during deep dives by distributing the force over a larger area.
59:49 Broader Implications: The study highlights the remarkable diversity of parasite adaptations and the value of curiosity-driven research in potentially explaining phenomena like the rarity of insects in ocean environments. The key takeaway from this paper is summarized as "the deeper the rounder."