Sera from patients with active pulmonary tuberculosis and their household contacts induce nuclear changes in neutrophils

Mario Juárez-Ortega,1 Oscar Rojas-Espinosa,1 Raquel Muñiz-Salazar,2 Enrique Becerril-Villanueva,3 Alejandro Hernández-Solís,4 Patricia Arce-Paredes,1 Sergio Islas-Trujillo,1 Raúl Cicero-Sabido4 1Department of Immunology, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Mexico City, Mexico; 2School of Health Sciences, Unidad Ensenada, Universidad Autónoma de Baja California, Ensenada, BC, Mexico; 3Laboratory of Psychoimmunology, Dirección de Investigaciones en Neurociencias, Instituto Nacional de Psiquiatría Ramón de la Fuente, Mexico City, Mexico; 4Pneumology Unit, Hospital General de México “Eduardo Liceaga”, UNAM, Mexico City, Mexico Background: Resident alveolar macrophages, dendritic cells, and immigrating neutrophils (NEU) are the first cells to contact Mycobacterium tuberculosis in the lung. These cells, and additional lymphoid cells in the developing granuloma, release a series of components that may concentrate in the serum and affect disease progression. Purpose: The aim of this study was to investigate the effect of the serum from tuberculosis (TB) patients and their household contacts (HHC) on the nuclear morphology of NEU. Materials and methods: NEU from healthy (HLT) people were incubated with sera from patients with active pulmonary TB, their HHC, and unrelated people. Changes in the nuclear morphology of NEU were analyzed by light and electron microscopy. Results: Sera from patients with TB induced changes in the nuclear morphology of NEU that included pyknosis, swelling, apoptosis, and netosis in some cases. Sera from some HHC induced similar changes, while sera from HLT people had no significant effects. Bacteria did not appear to participate in this phenomenon because bacteremia is not a recognized feature of nonmiliary TB, and because sera from patients that induced nuclear changes maintained their effect after filtration through 0.22 µm membranes. Neither anti-mycobacterial antibodies, TNFα, IL-6, IFNγ, or IL-8 participated in the phenomenon. In contrast, soluble mycobacterial antigens were likely candidates, as small quantities of soluble M. tuberculosis antigens added to the sera of HLT people led to the induction of nuclear changes in NEU in a dose-dependent manner. Conclusion: These results might help to detect subclinical TB within HHC, thus leading to a recommendation of prophylactic treatment. Keywords: tuberculosis, serum, neutrophils, pyknosis, apoptosis, netosi