Publications by authors named "Tais Saito"
Article Synopsis
- The study focuses on improving human immune system (HIS) mouse models for HIV research, using a method to enhance lymph node and circulating T cell levels through the injection of a specific human ligand (rFLT-3 L).* -
- The treatment with the Caspase-1/4 inhibitor VX-765 showed promise in reducing CD4 T cell loss and lowering viral load in key lymphoid tissues, coupled with evidence of decreased viral RNA levels.* -
- These findings suggest that manipulating immune system characteristics in HIS mice can aid in understanding HIV pathology and developing host-directed therapies, although more work is needed to optimize the model further.*
We previously reported that microRNA (miR)23a and miR30b are selectively sorted into exosomes derived from rickettsia-infected endothelial cells (R-ECExos). Yet, the mechanism remains unknown. Cases of spotted fever rickettsioses have been increasing, and infections with these bacteria cause life-threatening diseases by targeting brain and lung tissues.
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- Researchers found that specific microRNAs (miR23a and miR30b) are packed into exosomes from rickettsia-infected endothelial cells, but they're still uncovering how this happens.
- The study highlights that these exosomes disrupt important cell junctions in microvascular endothelial cells, leading to barrier dysfunction in lung cells, which can be harmful.
- Analysis revealed that these microRNAs are selectively enriched in the exosomes, indicating a potential link between their levels and the harmful effects caused by rickettsia infections.
Article Synopsis
- - Heterologous vaccine regimens, like using peptide nanofibers (PNFs) with an Ag85B epitope, may help boost immunity in people vaccinated with BCG, especially by enhancing T cell response in mice.
- - The study found that using dendritic cells pulsed with these PNFs increased not only the number of memory CD4 T cells but also their functional abilities, indicating a potential for improved immune responses.
- - However, a single boost of Ag85B PNF in BCG-primed mice did not show a reduction in lung infection after exposure to Mtb, pointing to the need for new BCG booster strategies that effectively activate tissue-resident memory cells.
Article Synopsis
- - The study investigates how intracellular cAMP receptor exchange proteins influence the ability of rickettsial bacteria to adhere to and invade vascular endothelial cells, aiming to clarify the mechanisms involved in this process.
- - Researchers utilized a unique in vivo system combined with fluidic force microscopy to analyze bacterial adhesion, finding that the absence of a specific gene significantly reduces rickettsial binding to endothelial cells.
- - Results indicated that rickettsial protein OmpB has variable binding strength depending on the host, and phosphorylation at a specific site (Y23) plays a crucial role in modulating this adhesion, suggesting that the cAMP signaling pathway is key in rickettsial infection.
Article Synopsis
- Coagulopathy, which involves problems with blood clotting, is linked to inflammation and infections like COVID-19 caused by SARS-CoV-2, indicating a complex relationship between these conditions.
- A protein called von Willebrand factor (vWF) is released during inflammation, and its secretion is regulated by EPAC1, an intracellular receptor that generally helps suppress inflammation.
- Studies using EPAC1-deficient mice showed that without EPAC1, there was increased vWF release during inflammation, suggesting that targeting EPAC1 could be a new approach to managing blood clotting issues associated with inflammatory conditions.
Article Synopsis
- Tuberculosis (TB) is influenced by how macrophages' pattern recognition receptors respond to mycobacterial infection, affecting inflammation and antimicrobial actions.
- The study shows that the macrophage galactose-type lectin (MGL)-1 plays a crucial role in modulating immune responses in a mouse model of TB, with its absence leading to increased inflammation and lipid accumulation.
- MGL-1 also exhibits unexpected antimycobacterial activity, suggesting that targeting the MGL pathway could offer new therapeutic approaches for enhancing anti-TB immunity.
Article Synopsis
- Spotted fever group rickettsioses (SFRs) are severe infections primarily affecting vascular endothelial cells, leading to harmful edema in the brain and lungs.
- This study investigated the role of exosomes (Exos) derived from infected endothelial cells and mouse plasma in the dysfunction of brain microvascular endothelial cells (BMECs).
- Findings revealed that rickettsial infection increased the release of specific exosomes which negatively impacted BMEC barrier function, highlighting the importance of exosomal RNA cargo in this process.
Article Synopsis
- * The exchange protein directly activated by cAMP (EPAC) is crucial for stabilizing endothelial cells and controlling inflammation; its absence leads to increased vWF release during inflammation.
- * The study found that EPAC1's regulation of vWF secretion operates through the PI3K/eNOS pathway, indicating that targeting this pathway could be a strategy for managing thrombosis during inflammatory conditions.
Intracerebral microhemorrhages (CMHs) are small foci of hemorrhages in the cerebrum. Acute infections induced by some intracellular pathogens, including rickettsia, can result in CMHs. Annexin a2 (ANXA2) has been documented to play a functional role during intracellular bacterial adhesion.
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- Tuberculosis (TB) relapse after drug treatment poses significant public health challenges, particularly due to worse health outcomes and the risk of drug resistance.
- Co-infection with HIV, even in those on anti-retroviral therapy, increases the risk of TB relapse and the spread of drug-resistant strains.
- Researchers used humanized mice to study TB relapse following chemotherapy in the context of HIV infection, revealing changes in lung pathology and viral replication patterns that could enhance understanding of the disease mechanisms and aid in creating new clinical interventions.
Talin and vinculin, both actin-cytoskeleton-related proteins, have been documented to participate in establishing bacterial infections, respectively, as the adapter protein to mediate cytoskeleton-driven dynamics of the plasma membrane. However, little is known regarding the potential role of the talin-vinculin complex during spotted fever group rickettsial and Ebola virus infections, two dreadful infectious diseases in humans. Many functional properties of proteins are determined by their participation in protein-protein complexes, in a temporal and/or spatial manner.
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- The study investigates how a high-fat diet (HFD) affects subcutaneous adipose tissue (scAT) and peripheral blood mononuclear cells (PBMC) over time, using rabbits as a model.
- Results showed that HFD caused changes in the blood cells of rabbits after 5 weeks, increasing inflammation and contributing to insulin resistance by 10 weeks, but did not significantly alter the scAT's lipid metabolism or inflammation.
- The findings suggest that targeting the inflammatory responses in PBMC could be crucial for preventing metabolic issues associated with obesity and improving health outcomes.
Article Synopsis
- Researchers aimed to study rickettsial infections, particularly focusing on the interactions between ticks, hosts, and the bacteria during tick feeding.
- A suitable mouse strain (C3H/HeN) was identified for experiments involving the emerging pathogen, Rickettia parkeri, transmitted by Amblyomma maculatum ticks.
- Results revealed that after tick attachment, the bacteria spread quickly throughout the body, causing significant inflammation and tissue damage by day 6, demonstrating the potential of this model for further research on rickettsial diseases.
Rift Valley fever phlebovirus (RVFV) causes high rates of abortions and fetal malformations in ruminants, and hemorrhagic fever, encephalitis, or blindness in humans. Viral transmission occurs via mosquito vectors in endemic areas, which necessitates regular vaccination of susceptible livestock animals to prevent the RVF outbreaks. Although ZH501 strain has been used as a challenge strain for past vaccine efficacy studies, further characterization of other RVFV strains is important to optimize ruminant and nonhuman primate RVFV challenge models.
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- Nipah virus (NiV) is a zoonotic virus that can cause severe respiratory illness or brain infections in humans, but its mechanisms of inducing acute lung injury are not fully understood.
- Research involving human lung grafts in a special type of mouse model demonstrated that NiV-B can replicate in these grafts and trigger significant inflammatory responses, regardless of the human immune cell presence.
- The findings revealed that while human immune cells did not prevent NiV replication, they played a role in limiting the virus's spread, increasing immune cell migration to the lungs, and elevating inflammatory markers, thus influencing the lung injury response.
Article Synopsis
- Ehrlichioses are diseases caused by intracellular bacteria that live within a tick vector and persist in vertebrate hosts, leading to severe illnesses in incidental hosts.* -
- The bacteria manipulate host cells by secreting proteins that interfere with the immune response, causing severe disease through overactive immunological responses, particularly via TNF-α production.* -
- Vaccine development is difficult due to the bacteria's diverse antigens, the need to prevent harmful immune reactions, and a limited understanding of key protective antigens.*
Rickettsiae actively escape from vacuoles and replicate free in the cytoplasm of host cells, where inflammasomes survey the invading pathogens. In the present study, we investigated the interactions of Rickettsia australis with the inflammasome in both mouse and human macrophages. R.
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- Ehrlichioses are tick-borne diseases gaining attention worldwide, and this study aimed to create a natural infection model using a human pathogen called Ehrlichia muris-like agent (EMLA).
- Researchers fed Ixodes scapularis larvae on EMLA-infected mice, resulting in high infection rates in nymphs that later infested naive animals.
- The study found that while most animals developed infections, with some fatalities, the tick transmission model led to stronger immune responses than traditional needle inoculation methods, marking a significant advancement in understanding these diseases.
Article Synopsis
- Orientia tsutsugamushi is the bacteria causing scrub typhus, spread by larval trombiculid mites, with about one-third of the global population at risk, highlighting its significance in health.
- The Karp strain of Orientia has been used in mouse studies but has struggled to replicate severe human disease, prompting researchers to create a more effective model.
- The new intravenous infection model in C57BL/6 mice resulted in disease symptoms and pathology similar to human scrub typhus, allowing for better understanding of immunity and disease mechanisms.
Article Synopsis
- Researchers developed a mouse model for studying ehrlichiosis using the human pathogen Ehrlichia muris-like agent (EMLA) to better understand this tick-borne disease.* -
- Three strains of mice were infected with EMLA via different methods, revealing that infection severity varied based on the route and dose, with effects similar to human infections.* -
- The new EMLA mouse model shows promise for investigating disease mechanisms, immune responses, and transmission of ehrlichiosis.*
Article Synopsis
- Anaplasmosis and ehrlichiosis, caused by various tick-borne bacteria, are emerging diseases affecting both dogs and humans, with more understanding in canines than in humans.
- Researchers used serology and PCR methods to test blood samples from family members and their dog for these infections.
- The study found DNA of A. platys and Ehrlichia in asymptomatic individuals, highlighting the need for awareness of potential co-infections in both pets and their owners.
Article Synopsis
- Ehrlichioses are tick-borne bacterial diseases with no available vaccines, caused by intracellular bacteria from the Ehrlichia genus; various immunoreactive proteins play a role in the immune response.
- In a study, the protein E. muris P29 was evaluated as a subunit vaccine in mice and showed significant protection against challenge infections, contrasting with other Ehrlichia proteins that contained tandem repeats.
- The successful immunization with E. muris P29 led to strong antibody responses, particularly IgG, highlighting the role of CD4+ T cells in targeting the protein during infection, while persistent infection impaired the IgG antibody response.
Article Synopsis
- The bacterium Ehrlichia chaffeensis causes human monocytotropic ehrlichiosis (HME), a serious tick-borne disease in the U.S.
- Current strategies for combating HME focus on the immune response, specifically activating CD4(+) and CD8(+) T cells, but there are no available vaccines.
- A study using proteins from a related bacterium, Ehrlichia muris, found that specific outer membrane proteins can generate long-term immune responses and reduce bacterial loads in vaccinated mice, highlighting the potential for new vaccine development.