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Co-infections with respiratory virus and Streptococcus pneumoniae have been frequently reported in epidemiologic studies. Here, we explore how inoculating A549 and Hep-2 cell monolayers with human metapneumovirus (hMPV) affected subsequent in vitro infections with pneumococcus serotypes 3 and 14. The different serotypes had variable adherence, but the A549 cells with a preceding hMPV infection had significantly enhanced bacterial adherence. Also, BALB/c mice infected with hMPV had increased adhesion of pneumococcus to the bronchial epithelium. The lungs of mice with a preceding hMPV inoculation had delayed bacterial clearance and exacerbated histopathology after they were infected with Streptococcus pneumoniae. Additionally, the mice with a preceding hMPV infection had inhibited recruitment of airway neutrophil and decreased expression of neutrophil chemoattractants. Our results suggest that airways infected with hMPV, especially lower airway epithelium, allow increased adherence of Streptococcus pneumoniae and hMPV-infected mice have impaired recruitment of airway neutrophils that may cause delayed bacterial clearance and exacerbated pulmonary inflammation.

Abstract Objective Develop a consensus for the nomenclature and definition of adrenal histopathologic features in unilateral primary aldosteronism (PA). Context Unilateral PA is the most common surgically treated form of hypertension. Morphologic examination combined with CYP11B2 (aldosterone synthase) immunostaining reveals diverse histopathologic features of lesions in the resected adrenals. Patients and Methods Surgically removed adrenals (n = 37) from 90 patients operated from 2015 to 2018 in Munich, Germany, were selected to represent the broad histologic spectrum of unilateral PA. Five pathologists (Group 1 from Germany, Italy, and Japan) evaluated the histopathology of hematoxylin-eosin (HE) and CYP11B2 immunostained sections, and a consensus was established to define the identifiable features. The consensus was subsequently used by 6 additional pathologists (Group 2 from Australia, Brazil, Canada, Japan, United Kingdom, United States) for the assessment of all adrenals with disagreement for histopathologic diagnoses among group 1 pathologists. Results Consensus was achieved to define histopathologic features associated with PA. Use of CYP11B2 immunostaining resulted in a change of the original HE morphology-driven diagnosis in 5 (14%) of 37 cases. Using the consensus criteria, group 2 pathologists agreed for the evaluation of 11 of the 12 cases of disagreement among group 1 pathologists. Conclusion The HISTALDO (histopathology of primary aldosteronism) consensus is useful to standardize nomenclature and achieve consistency among pathologists for the histopathologic diagnosis of unilateral PA. CYP11B2 immunohistochemistry should be incorporated into the routine clinical diagnostic workup to localize the likely source of aldosterone production.