Study: Host transcriptomic profiling of CD-1 outbred mice with severe clinical outcomes following infection with Orientia tsutsugamushi Image Credit: Anestial / Shutterstock

Scientists develop preclinical model of stunted typhus disease

The scientists developed an animal model of stunted typhus using ancient CD-1 mice. Using the model, they characterized the host susceptibility to the causative pathogen, disease pathogenesis, and immune responses. The research was published in the journal PLOS Neglected Tropical Diseases.

Studies: Host a transcriptomic profile of non-CD-1 bred mice with severe clinical consequences following infection with Orientia tsutsugamushi. Image Credit: Anestial / Shutterstock

Background

Scrub typhus is a vector-borne disease caused by an obligate intracellular Gram-negative bacterium. eastern tsutsugamushi. Bacteria typically multiply in the cytosol of endothelial cells and phagocytes and are transmitted by mites.

Hard typhus is quite common in the ‘Tsutsugamushi triangle’ of Southeast Asia. However, some cases have recently been detected in other geographic locations, including India, Nepal, Micronesia, Maldives, South America, the Middle East and Africa.

The infection is primarily self-limited with minor symptoms, including skin lesions, fever, and other flu-like symptoms. However, in severe cases, patients may develop pneumonia, liver inflammation, and meningoencephalitis, which can result in severe tissue damage, multi-organ failure, and even death.

Despite these intensities, eastern tsutsugamushi The infection continues to be neglected worldwide due to the lack of vaccines and proper diagnostic methods.

In the current study, scientists developed a next-generation mouse model. eastern tsutsugamushi Infection using CD-1 mice.

previous studies investigating eastern tsutsugamushi infection used natural mouse models. However, these models are not suitable for examining the effect of genetic variation on the clinical course. eastern tsutsugamushi infection.

Susceptibility of bred mice eastern tsutsugamushi infection

Study compared eastern tsutsugamushi Infection susceptibility of innate (B6) and exogenous (CD-1) mice. In both mouse models, eastern tsutsugamushi by intravenous injection.

The findings revealed that eastern tsutsugamushi Infection is 90-100% lethal in inbred mice compared to inbred mice (0-10%). Additionally, the new-generation mice had higher bacterial loads in several organs, including the lungs, spleen, kidney, and liver, than natural mice. Overall, these observations suggest that unmated mice are more susceptible to disease. eastern tsutsugamushi infection and they develop a systemic infection.

pathological changes eastern tsutsugamushi infection

Infected old mice eastern tsutsugamushi Pulmonary edema, interstitial pneumonia, perivascular lymphocytic infiltrates and vasculitis developed, which are the primary pathological features of severe cases. eastern tsutsugamushi infection in humans.

Binding of angiopoietin 1 (Ang1) to the cell surface receptor Tie2 is required to maintain vascular barrier integrity. During infection, this integrity is disrupted by Ang2, which binds to the Tie2 receptor to block the physiological Ang1–Tie2 axis.

In immature mice, eastern tsutsugamushi infection induced expression of Ang2 and decreased expression of Ang1 and Tie2. These observations indicate endothelial disruption and loss of vascular barrier integrity.

immune response eastern tsutsugamushi infection

lung immune response eastern tsutsugamushi infection was assessed in the study by performing differential analysis of 562 immunology-related genes in lung tissues.

The findings revealed a type 1 T helper cell/CD8-distorted response. eastern tsutsugamushi infection in new generation mice. In addition, significantly increased expressions of various proinflammatory mediators and cytotoxicity-related genes were observed in the next generation mice.

Significantly increased endothelial activation markers and receptor expressions were observed in lung tissues of infected next-generation mice. Markers of cellular stress and cytotoxicity were upregulated in the next generation of mice, with macrophage scavengers and C-type lectin receptors showing an overregulated expression.

Overall, these observations suggest that macrophage-induced C-type lectin (mince), an innate immune receptor that plays a vital role in sensing eastern tsutsugamushi infectious and stimulating type 1 cytokines and chemokines.

Significantly increased levels of several cytokines and chemokines were observed in serum samples collected from infected outbred mice, and this correlates with immune cell recruitment during the progression of the infection. The magnitude of the serum inflammatory response was much lower in congenital mice.

Overall, these observations suggest that vaccinated mice exhibit potent inflammatory responses for immune cell recruitment during progression to severe infection.

importance of study

The study identifies vaccinated mice CD-1 as a potent preclinical model of typhus. Mice are very sensitive eastern tsutsugamushi mimics infection and serious pathological features. eastern tsutsugamushi-infected people.

As the scientists noted, CD-1 mice could serve as a potential mouse model to study. eastern tsutsugamushi infection pathogenesis and related immune dysregulation. Additionally, this preclinical model could be useful for translational and vaccine development studies.

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