# Human Brain Organoid: a new CNSTB model

> **NIH NIH R56** · UNIVERSITY OF WISCONSIN-MADISON · 2021 · $649,083

## Abstract

PROJECT SUMMARY/ABSTRACT
Tuberculosis (TB) of the central nervous system (CNS) is the most dangerous form of M. tuberculosis (Mtb)
infection. For these cases, the risk of mortality is extremely high; those who survive are left with an elevated risk
of severe neurological damage and disability. Despite its public health importance, current understanding of the
dissemination of Mtb in the brain and anti-mycobacterial immunity within the human brain parenchyma is limited.
This represents a roadblock for developing a better cure for TB meningitis. This concern motivated the NIH to
organize a TB Meningitis workshop to develop a roadmap for advancing CNS TB research. The workshop
established that creating human in vitro platforms would facilitate research on the field and significantly contribute
to the understanding of cellular and molecular insights into the pathogenesis of CNS TB. This proposal will test
and optimize a new platform, Mtb infection of human brain organoids, to study CNS Mtb infection.
Previously, we have found that mycobacterial infection of the murine brain leads to protective immune responses
and bacterial control. While useful, murine model systems do not always reflect the many aspects of human
disease, and the application of human single and multi-component neuronal tissues would be more appropriate.
Mtb infects phagocytes, and most of the Mtb in the brain after CNS infection is located in recruited monocytes
and local microglia. We discovered that neural progenitors could also be infected with Mtb. Under this proposal's
aegis, we will test how the different infected phagocytes contribute to brain tuberculosis.
The two main objectives of this proposal are to understand the mechanism and consequences of bacterial
uptake by neural progenitors (Aim 1) and to apply neuronal organoids to test mechanisms of Mtb dissemination
and brain cell responses to Mtb infection. We propose to compare the effects of different Mtb-infected phagocytes
on human neural tissue (Aims 2 and 3).
Successful completion of this work will lead to new knowledge on a novel aspect of brain TB concerning
neural progenitors' infection. It raises the possibility that Mtb effects neuronal replacement at sites
where neurons are constitutively generated. In addition, we develop new human model platforms to
study the dissemination of Mtb into the brain and brain-specific responses to Mtb infection.

## Key facts

- **NIH application ID:** 10453987
- **Project number:** 1R56AI162164-01
- **Recipient organization:** UNIVERSITY OF WISCONSIN-MADISON
- **Principal Investigator:** Matyas Sandor
- **Activity code:** R56 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $649,083
- **Award type:** 1
- **Project period:** 2021-08-19 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10453987

## Citation

> US National Institutes of Health, RePORTER application 10453987, Human Brain Organoid: a new CNSTB model (1R56AI162164-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10453987. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*