  Citation: Trousil, J.; Frgelecová, L.; Kubíˇ cková, P.; ˇ Reháková, K.; Drašar, V.; Matˇ ejková, J.; Štˇ epánek, P.; Pavliš, O. Acute Pneumonia Caused by Clinically Isolated Legionella pneumophila Sg 1, ST 62: Host Responses and Pathologies in Mice. Microorganisms 2022, 10, 179. https://doi.org/10.3390/ microorganisms10010179 Academic Editors: Jean-Marc Berjeaud and Julien Verdon Received: 14 December 2021 Accepted: 12 January 2022 Published: 14 January 2022 Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affil- iations. Copyright: © 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/). microorganisms Article Acute Pneumonia Caused by Clinically Isolated Legionella pneumophila Sg 1, ST 62: Host Responses and Pathologies in Mice Jiˇ rí Trousil 1, * ,† , Lucia Frgelecová 2,† , Pavla Kubí ˇ cková 3 , Kristína ˇ Reháková 4 , Vladimír Drašar 5 , Jana Mat ˇ ejková 6 , Petr Št ˇ epánek 1 and Oto Pavliš 3 1 Institute of Macromolecular Chemistry, Czech Academy of Sciences, Heyrovského nám. 2, 162 00 Prague, Czech Republic; stepanek@imc.cas.cz 2 Department of Pathological Morphology and Parasitology, Faculty of Veterinary Medicine, University of Veterinary Sciences Brno, Palackého tˇ r. 1946/1, 612 42 Brno, Czech Republic; frgelecoval@vfu.cz 3 Military Health Institute, Military Medical Agency, Tychonova 1, 160 00 Prague, Czech Republic; pafcule@centrum.cz (P.K.); oto.pavlis@email.cz (O.P.) 4 Small Animal Clinical Laboratory, Faculty of Veterinary Medicine, University of Veterinary Sciences Brno, Palackého tˇ r. 1946/1, 612 42 Brno, Czech Republic; rehakovak@vfu.cz 5 National Legionella Reference Laboratory, Public Health Institute Ostrava, Masarykovo námˇ estí 16, 682 01 Vyškov, Czech Republic; Vladimir.Drasar@zuova.cz 6 Department of Medical Microbiology, Second Faculty of Medicine, Charles University, Motol University Hospital, V Úvalu 84, 150 06 Prague, Czech Republic; jana.matejkova@fnmotol.cz * Correspondence: jiri.trousil@centrum.cz or trousil@imc.cas.cz † These authors contributed equally to this work. Abstract: Legionnaires’ disease is a severe form of lung infection caused by bacteria belonging to the genus Legionella. The disease severity depends on both host immunity and L. pneumophila virulence. The objective of this study was to describe the pathological spectrum of acute pneumonia caused by a virulent clinical isolate of L. pneumophila serogroup 1, sequence type 62. In A/JOlaHsd mice, we compared two infectious doses, namely, 10 4 and 10 6 CFU, and their impact on the mouse status, bacterial clearance, lung pathology, and blood count parameters was studied. Acute pneumonia resembling Legionnaires’ disease has been described in detail. Keywords: legionellosis; histopathology; A/J mouse; lung infection; mouse model; inflammatory 1. Introduction Geographically, infectious diseases spread much faster now than at any time in history, and they continue to cause significant morbidity and mortality in human populations as well as economic disruption [1,2]. Taking bacterial infections as an example, humankind has been facing a crisis of antibiotic resistance because of the overuse and misuse of antibiotics. Bacterial pathogens can grow rapidly into biofilms that block the diffusion of antibiotics and thereby represent a public health problem. Some bacterial species, so-called intracellular bacteria, have acquired a complex and intricate ability to “hide” in mammalian cells, such as macrophages, thereby preventing antibiotics from destroying hidden pathogens and further increasing the challenges of therapy [3]. Legionella pneumophila is an emerging facultative intracellular bacterium that lives in both water and soil. It proliferates intracellularly, mostly in protozoa, including amoe- bae and ciliates. Once contaminated water droplets are inhaled by a human host, the bacteria reach the pulmonary alveoli, where they are phagocytized by resident alveolar macrophages. Depending on the host immunity and L. pneumophila virulence, the infec- tion may progress to severe acute pneumonia, which is called Legionnaires’ disease, a milder illness called Pontiac fever, and possibly bacteremia resulting in extrapulmonary manifestations [4,5], including myocarditis, acute disseminated encephalomyelitis, and Microorganisms 2022, 10, 179. https://doi.org/10.3390/microorganisms10010179 https://www.mdpi.com/journal/microorganisms