Spatial transcriptomics reveals early immune responses in HIV and tuberculosis coinfection in humanized mice
Abstract
Mycobacterium tuberculosis (Mtb) and human immunodeficiency virus (HIV) coinfection is a major public health concern, yet early immune and tissue changes during coinfection remain incompletely understood. Here we show, using a humanized mouse model and spatial transcriptomics of lung tissue, that early immune cell infiltration differs across single and combined infections. Mtb infection is associated with increased CD4 positive T cell infiltration, whereas this response is reduced in HIV infection and coinfection. Coinfected lungs also show lower natural killer cell abundance. Spatial profiling identifies distinct airway regions with different immune cell compositions and a lymphoid aggregate in coinfected lung with a distinct transcriptional profile. Although this aggregate lacks the cellular organization of a mature granuloma, it exhibits granuloma-associated gene expression signatures and pathways related to reactive oxygen species production, oxidative phosphorylation, transforming growth factor beta signaling, and interferon signaling. These findings define early spatial immune changes associated with coinfection.
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BibTeX
@article{adduri2026spatial,
title = {{Spatial transcriptomics reveals early immune responses in HIV and tuberculosis coinfection in humanized mice}},
author = {Sitaramaraju Adduri and Jose Alejandro Bohorquez and Rajesh Mani and Leticia Guzman Ruiz and Priyanka Sharma and Omoyeni Adejare and Diego Rincon and Joshua K. Kleam and Mounika Duggineni and Andy Omeje and Torry Tucker and Nagarjun V. Konduru and Guohua Yi},
journal = {Communications Biology},
year = {2026},
month = oct,
doi = {10.1038/s42003-026-11077-z},
url = {https://www.nature.com/articles/s42003-026-11077-z},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Spatial transcriptomics reveals early immune responses in HIV and tuberculosis coinfection in humanized mice
AU - Sitaramaraju Adduri
AU - Jose Alejandro Bohorquez
AU - Rajesh Mani
AU - Leticia Guzman Ruiz
AU - Priyanka Sharma
AU - Omoyeni Adejare
AU - Diego Rincon
AU - Joshua K. Kleam
AU - Mounika Duggineni
AU - Andy Omeje
AU - Torry Tucker
AU - Nagarjun V. Konduru
AU - Guohua Yi
PY - 2026
DA - 2026/10/09
JO - Communications Biology
DO - 10.1038/s42003-026-11077-z
UR - https://www.nature.com/articles/s42003-026-11077-z
AB - Mycobacterium tuberculosis (Mtb) and human immunodeficiency virus (HIV) coinfection is a major public health concern, yet early immune and tissue changes during coinfection remain incompletely understood. Here we show, using a humanized mouse model and spatial transcriptomics of lung tissue, that early immune cell infiltration differs across single and combined infections. Mtb infection is associated with increased CD4 positive T cell infiltration, whereas this response is reduced in HIV infection and coinfection. Coinfected lungs also show lower natural killer cell abundance. Spatial profiling identifies distinct airway regions with different immune cell compositions and a lymphoid aggregate in coinfected lung with a distinct transcriptional profile. Although this aggregate lacks the cellular organization of a mature granuloma, it exhibits granuloma-associated gene expression signatures and pathways related to reactive oxygen species production, oxidative phosphorylation, transforming growth factor beta signaling, and interferon signaling. These findings define early spatial immune changes associated with coinfection.
SN - 2399-3642
ER -