The story began in March 2022, when the previously healthy man developed fever and a dry cough. Empirical antibiotics for suspected pneumonia achieved nothing. By April he had been admitted to hospital, where computed tomography revealed consolidation studded with ground-glass opacities in his left lower lobe. His blood work painted a picture of vigorous inflammation: a white cell count of 17,600 per microlitre with neutrophils dominating, and a C-reactive protein level of 15.0 milligrams per decilitre. Crucially, he carried a long-standing diagnosis of oesophageal achalasia, a rare motility disorder first treated with balloon dilation at age 35. Over the preceding five years his ability to swallow had deteriorated relentlessly, with worsening dysphagia and vomiting despite medical therapy.

Diagnostic certainty proved elusive. A single sputum culture yielded Mycobacterium fortuitum, but subsequent cultures were negative, and the findings did not satisfy standard criteria for established nontuberculous mycobacterial disease. The team initially diagnosed aspiration pneumonia complicated by secondary organising pneumonia, treating him with antibiotics and corticosteroids. Neither touched the disease. Then came an observation that would eventually unlock the diagnosis: his respiratory symptoms rose and fell in eerie synchrony with his gastrointestinal ones, flaring during bouts of vomiting and easing when the vomiting subsided. That temporal coupling, the clinicians reasoned, pointed toward chronic microaspiration as the engine of the lung disease.

When symptoms escalated again in April 2024, bronchoscopy was repeated. Histopathological examination of biopsy specimens from the left lower lobe revealed non-caseating granulomas, the characteristic immune structures of mycobacterial infection, and Ziehl-Neelsen staining demonstrated acid-fast bacilli directly within the tissue. Combined with the earlier positive culture, these findings fulfilled the current Japanese diagnostic criteria for pulmonary nontuberculous mycobacterial disease attributable to M. fortuitum driven by chronic aspiration secondary to achalasia. The authors acknowledge that a two-year gap separated the microbiological and histopathological evidence, but they argue that persistent symptoms, repeated parallel exacerbations, and tissue demonstrating granulomas with acid-fast organisms made transient colonisation or contamination implausible.

The therapeutic decision was the radical part. Recognising that control of the underlying oesophageal disorder was essential, the team performed peroral endoscopic myotomy, known as POEM, in October 2024. POEM is a minimally invasive procedure in which an endoscope tunnels through the oesophageal wall to divide the muscular fibres of the lower oesophageal sphincter, restoring the passage of food into the stomach. The effect on the patient’s achalasia was dramatic; his swallowing difficulties and vomiting improved markedly. But the lung outcome was the real headline. Without ever initiating antimycobacterial therapy, his cough and fever resolved, and follow-up imaging showed marked radiological improvement. More than a year after the procedure, no recurrence of pneumonia or mycobacterial disease had been observed, though mild residual fibrosis remains.

To appreciate why this matters, one must understand both organisms and mechanism. Mycobacterium fortuitum belongs to Runyon group IV, the rapidly growing nontuberculous mycobacteria, and is ubiquitous in soil and water. It most often causes skin, soft-tissue, catheter-related and postoperative infections, with pulmonary disease being distinctly uncommon and usually a secondary affair in people with structural lung disease or chronic aspiration. Achalasia, characterised by impaired relaxation of the lower oesophageal sphincter and absent peristalsis, produces stasis of food within a dilating oesophagus. Nontuberculous mycobacteria are commonly ingested with food and can colonise the upper gastrointestinal tract; in achalasia patients, repeated microaspiration of these retained contents seeds the airways. The association between achalasia and pulmonary nontuberculous mycobacterial infection has been recognised for decades, with rapidly growing species frequently implicated.

The authors add a provocative mechanistic twist: the lipid-rich environment within retained oesophageal contents may itself potentiate the pathogenicity of rapidly growing mycobacteria. Previous work has suggested that lipid conditions can impair macrophage phagocytosis and promote mycobacterial growth, effectively disarming one of the lung’s first lines of cellular defence. In this patient, the team notes that dietary habits favouring high-fat intake may have facilitated bacterial persistence, though they concede this remains speculative. If confirmed, the idea would give clinicians yet another reason to view oesophageal stasis not as a mere inconvenience but as an active contributor to pulmonary immunopathology.

How does this case compare with the medical literature? The authors compiled eleven previously reported cases of pulmonary nontuberculous mycobacterial infection associated with achalasia, spanning organisms from M. fortuitum and M. abscessus to M. thermoresistibile and M. wolinskyi. Virtually every patient required prolonged multidrug antimycobacterial regimens, often involving combinations of amikacin, imipenem, clarithromycin, fluoroquinolones, linezolid or other agents, in addition to endoscopic or surgical correction of the oesophagus. In contrast, the present patient achieved sustained clinical and radiological improvement through POEM alone. To the authors’ knowledge, this is the first reported case in which treating achalasia alone successfully controlled an established pulmonary nontuberculous mycobacterial infection, implying that eliminating chronic aspiration can restore effective host defence mechanisms capable of containing the infection without pharmacological help.

The authors are appropriately cautious about the limits of a single observational report. Causality cannot be definitively established: spontaneous fluctuation of disease activity or delayed effects of earlier treatments cannot be entirely excluded, though the tight temporal relationship between POEM and sustained improvement supports the aspiration hypothesis. A further limitation is the absence of microbiological follow-up, because once his respiratory symptoms resolved the patient could no longer produce sputum, so eradication of the organism could not be confirmed in cultures. Still, the clinical message is unambiguous. Clinicians should consider oesophageal achalasia as an underlying cause of pulmonary nontuberculous mycobacterial infection, particularly when respiratory symptoms fluctuate in step with gastrointestinal ones. In such patients, addressing the underlying motility disorder may be as important as any antibiotic, and in rare cases may be enough on its own to conquer the infection and prevent recurrence.

Subject of Research: A case report of pulmonary Mycobacterium fortuitum infection associated with oesophageal achalasia that improved after peroral endoscopic myotomy without antimycobacterial therapy.

Article Title: Pulmonary Mycobacterium fortuitum Infection Associated With Achalasia Treated With Peroral Endoscopic Myotomy Alone: A Case Report

Article References: Masuda, H., Torii, R., Yamasaki, K., Shingu, T., Hata, R., & Yatera, K. (2026). Pulmonary Mycobacterium fortuitum Infection Associated With Achalasia Treated With Peroral Endoscopic Myotomy Alone: A Case Report. Respirology Case Reports, 14(9), Article e70718. https://doi.org/10.1002/rcr2.70718

Image Credits: AI Generated

DOI: 10.1002/rcr2.70718

Keywords: Mycobacterium fortuitum, nontuberculous mycobacteria, achalasia, peroral endoscopic myotomy, chronic aspiration, pulmonary infection, POEM, respirology, case report, oesophageal motility disorder, Pulmonary, Mycobacterium

Non-tuberculous mycobacteria, often abbreviated NTM, are environmental organisms that increasingly cause chronic and debilitating lung disease worldwide. Among them, Mycobacterium abscessus stands out as particularly menacing. It is naturally resistant to many standard antibiotics, it can form ropelike cords that shield it from engulfment by immune cells, and it thrives in patients with pre-existing lung damage such as bronchiectasis, cystic fibrosis, or pulmonary fibrosis. Treatment regimens typically stretch for many months, involve multiple toxic drugs, and frequently fail to eradicate the infection. Against this grim clinical backdrop, the question of how the immune system naturally fights M. abscessus has remained surprisingly underexplored, particularly with respect to γδ T cells, an unconventional lymphocyte population whose role in NTM infection had never been systematically characterized.

γδ T cells differ from the conventional αβ T cells that dominate textbook immunology. Rather than recognizing peptide fragments presented by major histocompatibility molecules, they respond rapidly to a wide range of stress signals and microbial products, earning them a reputation as a bridge between innate and adaptive immunity. A major subset of these cells produces interleukin-17A, a powerful inflammatory cytokine best known for recruiting neutrophils and shaping defenses at body surfaces. To determine whether these cells matter in M. abscessus infection, the researchers built a mouse model of pulmonary infection and mapped the immune landscape of lung tissue over the early days of disease using single-cell RNA sequencing, a technique that captures the gene expression profile of thousands of individual cells simultaneously.

The single-cell atlas revealed a striking pattern. As infection took hold, γδ T cells accumulated in the lung and expanded a population that expressed high levels of IL-17A. When the team removed γδ T cells entirely, using mice genetically engineered to lack them, the consequences were dramatic: bacteria persisted at far higher levels in the lungs and spleens, and lung inflammation worsened. Conversely, when γδ T cells were depleted in animals that had already cleared a first infection and were then re-challenged, the protective advantage of prior exposure evaporated. These experiments established γδ T cells as indispensable players in the early defense against M. abscessus, a finding that had not been demonstrated before for any non-tuberculous mycobacterial pathogen.

Delving deeper, the investigators identified IL-17A itself as the linchpin of this protective response. Mice unable to produce IL-17A lost much of their capacity to control the infection, and importantly, the defect traced back to the γδ T cells themselves. Without IL-17A signaling, the cells became less adept at recognizing the bacterium and lost much of their cytotoxic firepower. In an elegant series of transfer experiments, IL-17A-deficient γδ T cells failed to protect infected animals, whereas their normal counterparts succeeded. This revealed something unusual: IL-17A was not merely acting as a broadcast signal to other immune players but was required within the γδ T cells themselves, a cell-intrinsic requirement that underscores how tightly the cytokine and its producer are wired together during this infection.

The mechanism by which these cells actually kill the bacterium proved to be equally instructive. M. abscessus is an extracellular pathogen during key phases of infection, residing outside host cells in the airways and tissue spaces. The researchers found that IL-17A-positive γδ T cells eliminated extracellular bacteria through a granzyme B-dependent cytotoxic pathway. Granzyme B is a serine protease classically associated with the destruction of virus-infected or malignant cells, delivered through pore-forming perforin or other release mechanisms. Its deployment against free-living bacteria adds a new dimension to the antimicrobial portfolio of γδ T cells and explains how a lymphocyte population usually discussed in the context of autoimmunity and inflammation can act as a direct bactericidal weapon.

How, then, does the immune system know to mobilize these cells in the first place? The answer lies in a cascade that begins with Toll-like receptor 2, a pattern-recognition receptor on macrophages that detects components of the bacterial cell wall. When M. abscessus engaged TLR2 on lung macrophages, the macrophages responded by secreting two cytokines, interleukin-1β and interleukin-23. This cytokine pair is a well-known stimulus for IL-17 production in T cells, and in this context it drove both the expansion and the activation of the IL-17A-positive γδ T cell population. Blocking either IL-1β or IL-23 in infected mice diminished the γδ T cell response and impaired bacterial control, mapping out a complete signaling axis that runs from bacterial recognition through macrophage activation to lymphocyte mobilization and, ultimately, bacterial killing.

Perhaps the most clinically resonant aspect of the study concerns patients whose immunity depends on interferon-gamma, the canonical cytokine for defense against mycobacteria. A subset of individuals, particularly in Southeast Asia, develops autoantibodies that neutralize their own interferon-gamma, leaving them exquisitely vulnerable to disseminated NTM infections. Using single-cell RNA sequencing of peripheral blood cells from NTM patients, the researchers found evidence that anti-interferon-gamma autoantibodies compromise γδ T cell function in humans, mirroring what they observed in mice lacking the interferon-gamma receptor. Crucially, in mice engineered without functional interferon-gamma signaling, IL-17A-positive γδ T cells still conferred protection, and the same held true in a model combining M. abscessus infection with bleomycin-induced pulmonary fibrosis. In other words, this arm of immunity operates independently of the interferon-gamma axis and remains effective even in scarred, damaged lungs.

The implications for therapy are considerable. Current treatment of NTM disease relies almost entirely on antibiotics that the pathogen is adept at resisting, and there are no licensed immunotherapies that bolster host defenses. If the pathways defined in this study can be harnessed in patients, whether by stimulating IL-1β and IL-23 signaling, expanding protective γδ T cell populations, or delivering IL-17A-driven cytotoxic activity directly, clinicians could gain a means of strengthening the lung’s own antimicrobial machinery. Such approaches would be especially valuable for the growing population of patients with anti-interferon-gamma autoantibodies or structural lung disease, for whom conventional regimens offer diminishing returns. The researchers caution that translating mouse findings to the clinic will require careful work, particularly because IL-17A is also implicated in inflammatory conditions such as psoriasis and could carry safety risks if induced systemically. Nevertheless, the identification of a concrete, mechanistically defined cell type that can clear M. abscessus marks a genuine advance. It transforms γδ T cells from immunological bystanders into a promising therapeutic target, and it reframes the fight against antibiotic-resistant mycobacteria as a battle that the immune system, with the right encouragement, may be able to win on its own terms.

Subject of Research: The role of IL-17A-producing γδ T cells in controlling pulmonary Mycobacterium abscessus infection in mice.

Article Title: IL-17A-producing γδ T cells control pulmonary Mycobacterium abscessus infection in mice

Article References: Hu, X., Lin, S., Meng, W., Liu, H., Qin, Z., Wu, Z., Wan, Y., Ma, S., Yang, X., Yin, Z., Chu, Y., Zhang, W., Shao, L., & Lin, Y. (2026). IL-17A-producing γδ T cells control pulmonary Mycobacterium abscessus infection in mice. Nature Microbiology. https://doi.org/10.1038/s41564-026-02466-5

Image Credits: AI Generated

DOI: 10.1038/s41564-026-02466-5

Keywords: Mycobacterium abscessus, non-tuberculous mycobacteria, γδ T cells, IL-17A, interferon-gamma, granzyme B, TLR2, IL-1β, IL-23, pulmonary infection, immunology, antibiotic resistance