Introduction: Mendelian susceptibility to mycobacterial disease (MSMD) is a rare and recently discovered primary immunodeficiency syndrome characterized by a predisposition to intracellular pathogens, non-tuberculous, and tuberculous mycobacteria. Recognition of this disease spectrum is important in guiding appropriate investigations and management. A 47-year-old Hmong female with a past history of remote pulmonary tuberculosis presented with fever, abdominal pain, and diarrhea for 3 days. Four months prior to this, she developed a bulky right cervical lymphadenopathy extending to the upper mediastinum. At that time, biopsy of the lymph node revealed necrotizing granulomatous inflammation and blood tests were pertinent for intermediate results of QuantiFERON-TB Gold and Salmonella O group B bacteremia, for which she completed a 14-day course of oral ciprofloxacin. Cultures of the lymph node yielded Histoplasma capsulatum, which was treated with intravenous amphotericin, followed by oral itraconazole. On initial exam, she was febrile and suffered from septic shock, and had a positive Murphy’s sign. Labs were pertinent for acute kidney injury, lactic acidosis, and no obstructive pattern on liver enzymes. Ultrasonography revealed acute cholecystitis, gallstones, sludge, and dilated common bile duct of 10 millimeters. The patient received antibiotics, biliary stenting, intraoperative cholangiogram, and subsequent cholecystectomy. Her blood cultures on this admission again grew Salmonella O group B. Her HIV status was unremarkable, normal CD4 counts, and T4/T8 ratio of 0.4 (0.8-3.7). Four months after this admission, she developed left-sided chest pain for 2 days with a new left supraclavicular lymphadenopathy causing isolated left internal jugular venous dilation. Biopsy of the lymph node was unremarkable, but both of blood cultures and the lymph node culture grew Mycobacterium avium intracellulare. She was treated with oral azithromycin, ethambutol, and intravenous amikacin. Molecular analysis of the interferon-gamma/interleukin-12 cascade revealed autoantibodies to interferon gamma. A defect in the interferon-gamma/interleukin-12 cascade should be suspected in patients who are vulnerable to recurrent systemic salmonellosis, extensive infections with mycobacterium, and intracellular pathogen, e.g. Histoplasma capsulatum. The spectrum is phenotypically described as MSMD, which is derived from Mendelian inheritance of defects in the cascade. This case also highlights an unusual presentation of MSMD as cholecystitis. Molecular and genetic analysis are required to define specific defect and possible treatment, e.g. interferon-gamma therapy and vaccinations, in addition to standard antibiotic regimens.