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Intestinal Microbiota Controls Graft-Versus-Host Disease Independent of Donor–Host Genetic Disparity

Koyama et al., Immunity. 2023.

https://pubmed.ncbi.nlm.nih.gov/37480848/

Allogeneic hematopoietic stem cell transplantation is a curative therapy for hematopoietic malignancies and non-malignant diseases, but acute graft-versus-host disease (GVHD) remains a serious complication. Specifically, severe gut GVHD is the major cause of transplant-related mortality. Here, the authors show that genetically identical mice, sourced from different vendors, had distinct commensal bacterial compositions, which resulted in significantly discordant severity in GVHD. These studies highlight the importance of pre-transplant microbiota composition for the initiation and suppression of immune-mediated pathology in the gastrointestinal tract, demonstrating the impact of non-genetic environmental determinants to transplant outcome. Supported by ORIP (S10OD028685), NIA, NCI, and NHLBI.

SARS-CoV-2 Infects Neurons and Induces Neuroinflammation in a Non-Human Primate Model of COVID-19

Beckman et al., Cell Reports. 2022.

https://www.doi.org/10.1016/j.celrep.2022.111573

SARS-CoV-2 causes brain fog and other neurological complications in some patients. It has been unclear whether SARS-CoV-2 infects the brain directly or whether central nervous system sequelae result from systemic inflammatory responses triggered in the periphery. Using a rhesus macaque model, researchers detected SARS-CoV-2 in the olfactory cortex and interconnected regions 7 days after infection, demonstrating that the virus enters the brain through the olfactory nerve. Neuroinflammation and neuronal damage were more severe in elderly monkeys with type 2 diabetes. The researchers found that in aged monkeys, SARS-CoV-2 traveled farther along nerve pathways to regions associated with Alzheimer's disease. Supported by ORIP (P51OD011107) and NIA.

Large Comparative Analyses of Primate Body Site Microbiomes Indicate That the Oral Microbiome Is Unique Among All Body Sites and Conserved Among Nonhuman Primates

Asangba et al., Microbiology Spectrum. 2022.

https://www.doi.org/10.1128/spectrum.01643-21

Microbiomes are critical to host health and disease, but large gaps remain in the understanding of the determinants, coevolution, and variation of microbiomes across body sites and host species. Thus, researchers conducted the largest comparative study of primate microbiomes to date by investigating microbiome community composition at eight distinct body sites in 17 host species. They found that the oral microbiome is unique in exhibiting notable similarity across primate species while being distinct from the microbiomes of all other body sites and host species. This finding suggests conserved oral microbial niche specialization, despite substantial dietary and phylogenetic differences among primates. Supported by ORIP (P51OD010425, P51OD011107, P40OD010965, R01OD010980), NIA, NIAID, and NICHD.

Monoclonal Antibodies Protect Aged Rhesus Macaques From SARS-CoV-2-Induced Immune Activation and Neuroinflammation

Verma et al., Cell Reports. 2021.

https://www.sciencedirect.com/science/article/pii/S2211124721014157?via%3Dihub%C2%A0=

In aged diabetic female rhesus macaques, prophylactic administration of neutralizing monoclonal antibodies (mAbs) effectively limits SARS-CoV-2 replication in both the upper and lower respiratory tract, and decreases immune activation, including reducing interferon-induced chemokines and limiting effector CD4 T cell influx into the cerebrospinal fluid. These protective mechanisms took place in the areas of the body targeted by the virus and may prevent adverse inflammatory consequences of SARS-CoV-2 infection in high-risk populations. Supported by ORIP (P51OD011107), NIAID, and NIA.