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Inflammatory responses revealed through HIV infection of microglia-containing cerebral organoids

Srinivas D Narasipura1, Janet P Zayas1, Michelle K Ash1

  • 1Department of Microbial Pathogens and Immunity, Rush University Medical Center, Chicago, IL, USA.

Journal of Neuroinflammation
|February 10, 2025
PubMed

Insights

Researchers developed novel microglia-containing cerebral organoids (CO-iMs) to model brain development and HIV-associated neuroinflammation. These organoids accurately mimic human brain cells and inflammatory responses in a 3D system.

Area of Science:

  • Neuroscience
  • Developmental Biology
  • Immunology

Background:

  • Cerebral organoids (COs) are crucial for studying brain development and disease.
  • HIV-associated neuroinflammation presents significant challenges in understanding brain pathology.
  • Existing models lack the cellular complexity to fully recapitulate in vivo brain microenvironments.

Purpose of the Study:

  • To develop a novel 3D model for studying microglia-neuron interactions in the brain.
  • To investigate HIV infection and neuroinflammation using a more physiologically relevant system.
  • To establish a robust platform for deciphering neuropathogenesis and viral infections.

Main Methods:

  • Co-culture of hematopoietic progenitors and induced pluripotent stem cells to generate microglia-containing cerebral organoids (CO-iMs).
  • Differentiation of microglia and neuronal progenitors within the organoids.
  • Assessment of microglial markers (CD45, CD11b, Iba-1), homeostatic markers, sensome markers, and complement cascade markers.
  • HIV infection model to evaluate pro-inflammatory cytokine/chemokine responses and the effect of antiretrovirals.

Main Results:

  • CO-iMs efficiently generated microglia (approx. 7%) with increased expression of homeostatic, sensome, and complement cascade markers.
  • CO-iMs exhibited increased pro-inflammatory cytokines/chemokines upon HIV infection.
  • Antiretroviral treatment abrogated the pro-inflammatory response in HIV-infected CO-iMs.
  • The model demonstrated susceptibility to HIV infection, mirroring aspects of neuropathogenesis.

Conclusions:

  • CO-iMs represent a robust and physiologically relevant 3D model for studying brain development, neuroinflammation, and viral infections.
  • This model facilitates the investigation of microglia-neuron interactions in conditions like HIV-associated neuroinflammation.
  • CO-iMs offer a valuable platform for testing therapeutic interventions against neuroinflammatory diseases and viral infections.
Keywords:
Cerebral organoidsHIVHPCIPSCMicrogliaNeuroinflammationNeuropathogenesis

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