Home›Nephrology› Respiratory viral coinfections reshape immune signaling and granuloma stability in Mycobacterium tuberculosis infections
Respiratory viral coinfections reshape immune signaling and granuloma stability in Mycobacterium tuberculosis infectionsViral Infections May Change How the Body Fights Tuberculosis
Frontiers in MedicinePublished July 4, 2026Study authors: Qaqamba Feya, Zilungile Lynette Mkhize-Kwitshana, Ridwaan Nazeer Milase, Ahmed Wadee, Natasha Naidoo…DOI ↗Editorial oversight: Dr. Amelia Tan, PhD · Internal Medicine & Chronic Disease
AI-generated summary of the cited source, checked by automated accuracy review.
How we work
Share
Key Takeaway
Note that respiratory viral coinfections may drive immune rewiring and granuloma instability in tuberculosis patients.
This narrative review explores the immunological consequences of coinfection between Mycobacterium tuberculosis and various respiratory viruses, such as SARS-CoV-2, influenza A/B, RSV, and others. The scope focuses on how these interactions influence host immune signaling pathways, granuloma stability, and subsequent tissue remodeling.
The authors synthesize findings indicating that innate sensing pathways, including TLR, RIG-I, and cGAS-STING, converge during coinfection to reshape IFN-I, NF-kB, and AP-1 responses. This immune rewiring is associated with altered granuloma stability through suppressed Th1/IFN-gamma coordination and exaggerated Th17/IL-17-driven neutrophilia. Furthermore, oxidative stress and mitochondrial dysfunction contribute to tissue remodeling, potentially leading to epithelial damage and fibrosis.
A primary limitation of this review is its nature as a narrative synthesis of existing literature rather than a systematic analysis of clinical trials. The authors note that specific clinical outcomes for individual viruses were not evaluated. These findings suggest a need for biomarker-guided host-directed therapies and timing-aware management for patients with concurrent infections, though the efficacy of specific host-directed therapies remains unproven.
How this fits prior evidence
This narrative review addresses gaps in understanding how respiratory viral coinfections impact tuberculosis outcomes. While prior coverage noted that video observed therapy improves treatment success and adherence in patients with tuberculosis, this review focuses on the underlying immunological mechanisms of coinfection. It does not provide data regarding the noninferiority of specific drug regimens or the efficacy of TCM for influenza mentioned in previous reports.
This review looked at what happens when a person is infected with both Mycobacterium tuberculosis and a respiratory virus, such as influenza, RSV, or SARS-CoV-2. The study focused on how these two infections interact within the body's immune system and the specific structures that contain the bacteria.
Researchers found that these combined infections can change how the immune system signals its response. Specifically, the presence of a virus can alter certain pathways that normally help fight infection. This shift can make it harder for the body to maintain stable defenses against tuberculosis, potentially leading to more tissue damage and scarring in the lungs.
Because this is a narrative review of existing literature rather than a clinical trial, these findings are not yet used to change standard medical treatments. The results suggest that doctors may eventually need to use specific markers to better manage patients who have both infections at once.
What this means for you:
Viral coinfections can alter immune responses and lung tissue health in people with tuberculosis.
Common questions
Which viruses are linked to changes in tuberculosis?
The review looked at several common respiratory viruses. These include SARS-CoV-2, influenza A and B, RSV, parainfluenza, metapneumovirus, rhinovirus, adenovirus, and bocavirus. Each of these can interact with the body's immune system when a patient also has a tuberculosis infection.
How does a viral infection affect the lungs during TB?
When both infections occur together, it can lead to oxidative stress and mitochondrial dysfunction. These factors can cause tissue remodeling, which may result in epithelial damage, cavitation, and fibrosis in the lung tissue.
What does this mean for current medical treatment?
This study is a narrative review of existing research rather than a new clinical trial. While it highlights how immune signals change during coinfection, it does not provide specific new treatments or proven outcomes for individual patients.
Tuberculosis (TB) caused by Mycobacterium tuberculosis (M. tuberculosis) and respiratory viral infections remain major, intersecting global health challenges, and their co-occurrence imposes a disproportionate burden in high-HIV/high-TB regions such as sub-Saharan Africa. Coinfection biology is heterogeneous and dynamic, driven by viral diversity including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), influenza A/B, Respiratory Syncytial Virus (RSV), parainfluenza, metapneumovirus, rhinovirus, adenovirus, and bocavirus, and by the underlying TB stage, from latent and subclinical to active and reactivation disease. Innate sensing pathways, such as Toll-like receptors (TLR), retinoic acid-inducible gene I (RIG-I), and cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS–STING), converge during coinfection, reshaping type I interferon (IFN-I), Nuclear Factor kappa-light-chain-enhancer of activated B cells (NF-κB), and AP-1–driven responses and triggering a network of autocrine and paracrine signaling that reprograms macrophages, dendritic cells, and T-cell subsets. This immune rewiring alters granuloma equilibrium through suppressed Th1/IFN-γ coordination, exaggerated Th17/IL-17-driven neutrophilia, and regulatory T-cell or IL-10-mediated dampening, which together destabilize macrophage activation and tissue architecture. Oxidative stress, mitochondrial dysfunction, and Matrix Metalloproteinases (MMP)-driven matrix remodeling further integrate with these pathways, converting inflammatory signals into epithelial damage, cavitation, and fibrosis. Consequently, disease outcomes depend critically on timing, viral burden, pathogen order, host immune endotype, and TB stage, such that the same virus can either preserve containment or drive progression depending on the local immunological context. Importantly, the effects of respiratory viral coinfection vary across the TB disease continuum, influencing early granuloma formation, latent infection, reactivation risk, and established disease through distinct immunological mechanisms. Host-directed therapies (HDT) targeting interferon, IL-1, TNF, inflammasome, or metabolic checkpoints hold mechanistic promise but exhibit variable clinical translation, underscoring the need for precision approaches that integrate stage- and endotype-specific biomarkers. This narrative review proposes an integrated systems framework that links viral sensing, immune rewiring, granuloma biology, and tissue-remodeling to TB–respiratory virus coinfection, and emphasizes how timing-aware, biomarker-guided strategies can refine diagnosis, clinical management, prognosis, and vaccine design in vulnerable populations.
