To defend against intracellular pathogens such as Toxoplasma gondii, the host generates a robust type 1 immune response. Specifically, host defense against T. gondii is defined by an IL-12–dependent IFN-γ response that is critical for host resistance. Previously, we demonstrated that host resistance is mediated by T-bet–dependent ILC-derived IFN-γ by maintaining IRF8+ conventional type 1 dendritic cells during parasitic infection. Therefore, we hypothesized that innate lymphoid cells are indispensable for host survival. Surprisingly, we observed that T-bet–deficient mice succumb to infection quicker than do mice lacking lymphocytes, suggesting an unknown T-bet-dependent–mediated host defense pathway. Analysis of parasite-mediated inflammatory myeloid cells revealed a novel subpopulation of T-bet+ myeloid cells (TMCs). Our results reveal that TMCs have the largest intracellular parasite burden compared with other professional phagocytes, suggesting they are associated with active killing of T. gondii. Mechanistically, we established that IL-12 is necessary for the induction of inflammatory TMCs during infection and these cells are linked to a role in host survival.

The obligate intracellular protozoan pathogen Toxoplasma gondii is estimated to infect a third of the world’s population. Toxoplasmosis is considered a significant worldwide disease that can lead to morbidity or death in immunocompromised individuals. Host defense against T. gondii has been demonstrated to be dependent on a rapid myeloid cell and lymphocyte response working in concert to quickly eliminate the invading pathogen. Classically, T-bet–dependent group 1 innate lymphocytes (ILC1s), natural killer (NK) cells, and CD4+ T cell–derived interferon-γ (IFN-γ) are considered indispensable for host resistance against T. gondii. However, recent discoveries have illustrated that T-bet is not required for NK cell– or CD4+ T cell–derived IFN-γ. Yet, lack of T-bet still results in rapid mortality, pointing to a T-bet–dependent myeloid cell–mediated host defense pathway. This review summarizes the myeloid cell–mediated immune response against T. gondii and provides insights into the lesser known components of the T-bet–dependent myeloid cell–dependent host defense pathway for pathogen clearance.

Background: Allograft failure after kidney transplantation remains common despite improving long-term outcomes and persistent organ scarcity. We aimed to develop and internally validate a perioperative risk model for kidney allograft failure within 2 years of transplantation. Methods: We conducted a single-center retrospective cohort study using the Medical Informatics Operating Room Vitals and Events Repository. Adult patients (≥18 years) undergoing kidney transplantation between January 2018 and July 2023 with at least 2 years of follow-up were included. The primary outcome was allograft failure within 2 years, defined as return to dialysis, pre-emptive re-transplantation, or death. Candidate predictors included demographic characteristics, comorbidities, preoperative laboratory values, and intraoperative variables. After univariate screening and variable selection with LASSO-penalized regression, we estimated relative risks using modified Poisson regression and assessed internal validity with 200 bootstrap resamples. Results: Among 319 recipients, 53 (16.6%) experienced early allograft failure. In the final multivariable model, obesity (relative risk [RR] 4.76; bootstrap 95% CI 2.88–9.31) and thrombocytopenia (RR 1.96; bootstrap 95% CI 1.18–3.38) were independently associated with increased risk. Anemia (RR 0.22; bootstrap 95% CI 0.13–0.37), preoperative clonidine use (RR 0.33; bootstrap 95% CI 0.00–0.85), and female sex (RR 0.55; bootstrap 95% CI 0.26–0.83) were associated with reduced risk. Model performance was modest (pseudo-R² 0.21) but identified clinically distinct risk strata. Conclusions: A five-variable perioperative model based on obesity, thrombocytopenia, anemia, preoperative clonidine use, and female sex identified kidney transplant recipients at differing risk of allograft failure within 2 years. These associations highlight potentially modifiable targets that warrant further study and external validation before clinical use.