1The Department of Infectious Diseases, State Key Laboratory for the Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for the Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, People’s Republic of China; 2Department of Medical Oncology, The Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, People’s Republic of China; 3Department of Gastroenterology and Infectious Diseases, Dongyang Hospital of Traditional Chinese Medicine, Jinhua, People’s Republic of China

Correspondence: Kaijin Xu, The Department of Infectious Diseases, State Key Laboratory for the Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for the Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, People’s Republic of China, Email [email protected] Jifang Sheng, The Department of Infectious Diseases, State Key Laboratory for the Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for the Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, People’s Republic of China, Email [email protected]

Abstract: We report a case of an adult male with a history of recurrent cough and chest pain for five years. Mycobacterium arosiense was identified in his alveolar lavage fluid, and whole-exome sequencing revealed heterozygosity for CD209 in this patient. After 17 months of combined antibiotic therapy, the patient recovered completely.

Case Introduction

A 26-year-old male, as an ordinary employee working in a corporate office, presented with a five-year history of recurrent cough and chest pain. Over the past two years, he had received intermittent treatment with various antibiotics, including moxifloxacin, imipenem cilastatin, and piperacillin tazobactam, with temporary improvement followed by relapse. A chest computed tomography (CT) scan revealed no abnormal lung lesions. Bronchoscopy showed patchy necrotic material covering the mucous membranes of the main trachea and bronchi. Tuberculosis skin tests and T-SPOT assays were negative. Most blood markers were within normal limits, and multiple microbiological tests on sputum, urine, stool, blood, and pharyngeal swabs were negative for bacteria and viruses. Next-generation sequencing (NGS) of bronchoalveolar lavage fluid identified Pseudomonas aeruginosa (sequence number 128043, relative abundance 99.24%) and M. arosiense (sequence number 268, relative abundance 0.21%). Based on these findings, the patient was diagnosed with bronchial infection due to M. arosiense and P. aeruginosa colonization and treated with rifampin, ethambutol, moxifloxacin, and azithromycin. His symptoms resolved, and he remained asymptomatic for over one year after completing 17 months of therapy. The microbiological cure was confirmed by NGS of bronchoalveolar lavage fluid after 3 years of therapy. Six bronchoscopies were performed to monitor endotracheal and endobronchial lesions (Figure 1).

Figure 1 Bronchoscopy of the patient during the therapy. (A) Bronchoscopy before therapy; (B) After 2 months of therapy; (C) After 4 months of therapy; (D) After 9 months of therapy; (E) After 17 months of therapy; (F) After 3 years of therapy.

Discussion

M. arosiense is a slow-growing, yellow-pigmented, scotochromogenic nontuberculous mycobacteria (NTM) species.1 It was first reported in 2008 in a young boy with hereditary partial gamma interferon receptor alpha-1 deficiency and osteomyelitic bone lesions.1 Clinically, M. arosiense is rarely encountered, and its identification often relies on advanced molecular techniques like metagenomic NGS (mNGS), which can detect all microorganisms in a sample.2

In vitro studies show that M. arosiense is sensitive to clarithromycin, rifamycins, amikacin, moxifloxacin, linezolid, and clofazimine but resistant to isoniazid, fluoroquinolones, and streptomycin.1 The young patient improved significantly after receiving a combination of rifampin, ethambutol, moxifloxacin, and azithromycin.

CD209, an autosomal dominant gene located on chromosome 19p13.3, encodes Dendritic Cell-Specific ICAM3-Grabbing Non-integrin (DC-SIGN), a C-type lectin expressed on dendritic cells and alveolar macrophages.3 DC-SIGN binds various ligands, including pathogens like Mycobacterium tuberculosis, HIV-1, and Dengue virus.4,5 It plays a critical role in Mycobacterium tuberculosis infection by facilitating internalization and immune suppression.6–8 The patient’s whole-exome sequencing revealed a heterozygous CD209 mutation (NM_021155.3:c.220C > T [p.Gln74*]), classified as a variant of uncertain significance.9,10 While CD209 promoter polymorphisms have been associated with infectious disease susceptibility, the relationship between CD209 mutations and NTM infections remains unclear.

This is the first reported case of pulmonary M. arosiense infection with a confirmed CD209 mutation. Previous cases have not explored genetic factors. However, there were also several limitations in this study. First, the sensitivity results of M. arosiense were lack. In addition, the exact functional impact of the CD209 mutation in relation to M. arosiense infection remains unclear. Therefore, further genetic testing in refractory NTM cases is warranted to investigate potential links between genetic mutations and specific infections.

Conclusion

This case highlights a rare instance of M. arosiense pneumonia in a patient with a CD209 mutation. While the patient responded well to antibiotic therapy, the role of the CD209 mutation in susceptibility remains uncertain. Further studies are needed to clarify the relationship between genetic factors and NTM infections.

Data Sharing Statement

This paper does not report data generation or analysis.

Ethics Approval and Consent to Participate

This study was conducted following the Declaration of Helsinki and obtained approval from the clinical research ethics committee of The First Affiliated Hospital, Zhejiang University School of Medicine [No. 20241303]. The patient gave written informed consent for his personal and clinical details along with any identifying images to be published in this study. The institutional approval was not required to publish the case details.

Consent to Publish

All authors have seen and approved the content.

Author Contributions

All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

Funding

This work was supported by the National Key R&D Program of China (2022 YFC2304505 and 2023YFC2306800) and Department of Health of Zhejiang province (2023XY037). The funder had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript.

Disclosure

The authors report no conflicts of interest in this work.

References

1. Bang D, Herlin T, Stegger M, et al. Mycobacterium arosiense sp. Nov. a slowly growing, scotochromogenic species causing osteomyelitis in an immunocompromised child. Int J Syst Evol Microbiol. 2008;58:2398–2402. doi:10.1099/ijs.0.65503-0

2. Pennington KM, Vu A, Challener D, et al. Approach to the diagnosis and treatment of non-tuberculous mycobacterial disease. J Clin Tuberc Other Mycobact Dis. 2021;24:100244. doi:10.1016/j.jctube.2021.100244

3. Tailleux L, Schwartz O, Herrmann JL, et al. Dc-sign is the major mycobacterium tuberculosis receptor on human dendritic cells. J Exp Med. 2003;197:121–127. doi:10.1084/jem.20021468

4. Gordon S. Pattern recognition receptors: doubling up for the innate immune response. Cell. 2002;111:927–930. doi:10.1016/S0092-8674(02)01201-1

5. van Kooyk Y, Geijtenbeek TB. Dc-sign: escape mechanism for pathogens. Nat Rev Immunol. 2003;3:697–709. doi:10.1038/nri1182

6. Geijtenbeek TB, Torensma R, van Vliet SJ, et al. Identification of dc-sign, a novel dendritic cell-specific icam-3 receptor that supports primary immune responses. Cell. 2000;100:575–585. doi:10.1016/S0092-8674(00)80693-5

7. Geijtenbeek TB, Van Vliet SJ, Koppel EA, et al. Mycobacteria target dc-sign to suppress dendritic cell function. J Exp Med. 2003;197:7–17. doi:10.1084/jem.20021229

8. Ortiz M, Kaessmann H, Zhang K, et al. The evolutionary history of the cd209 (dc-sign) family in humans and non-human primates. Genes Immun. 2008;9:483–492. doi:10.1038/gene.2008.40

9. Richards S, Aziz N, Bale S, et al. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American college of medical genetics and genomics and the association for molecular pathology. Genet Med. 2015;17:405–424. doi:10.1038/gim.2015.30

10. Barreiro LB, Neyrolles O, Babb CL, et al. Promoter variation in the dc-sign-encoding gene cd209 is associated with tuberculosis. PLoS Med. 2006;3:e20. doi:10.1371/journal.pmed.0030020