Vol. 14, No. 3 Printed in U.S.A.

INFECTION AND IMMUNITY, Sept. 1976, p. 832-835 Copyright ©) 1976 American Society for Microbiology

NOTES Morphology and Time Course of Experimental Listeriosis in Nude Mice B. HEYMER,* H. HOF, P. EMMERLING, AND H. FINGER Department ofPathology I, University of Ulm, Ulm, Germany,* and Institute of Hygiene and Microbiology,

University of Wurzburg, Wurzburg, Germany Received for publication 6 April 1976

Experimental listeriosis in phenotypically normal (nu/+) euthymic NMRI mice has a characteristic morphology and short-term course. In contrast, listeric infection in congenitally dysthymic nude (nu/nu) mice does not proceed in clearcut phases, develops more slowly, displays a chronic tendency from the beginning, and shows a considerably different morphology. The inability of nude mice to effectively control and terminate infection by Listeria monocytogenes obviously results from the lack of T lymphocytes. Listeria monocytogenes is a facultative intra- L. monocytogenes organisms, serotype 4 b. The cellular bacterial parasite that can survive and mean lethal intravenous dose in both dysmultiply in mammalian macrophages (7). Re- thymic and euthymic NMRI mice was approxisistance to infection with L. monocytogenes is mately 1 x 104 to 2 x 104 viable bacteria. Four based on cellular immune mechanisms: immu- to five mice out of each group were sacrificed 1, nity to this pathogen can only be transferred by 2, 3, 4, 7, 10, 14, 21, 28, and 35 days postinfecspecifically sensitized lymphocytes, not by se- tion (p.i.). At autopsy the liver, spleen, heart, rum (6-9). In addition to these thymus-derived lungs, kidneys, lymph nodes (abdominal, tho(T) lymphocytes, activated macrophages are re- racic), part of the small intestine (Peyer's quired for effective killing of L. monocytogenes patches), and all of the mediastinal tissues (7, 11, 12, 15). Surprisingly, nude mice with were removed, fixed in 4% buffered formalin, congenital dysplasia of the thymus (4, 10, 14) and embedded in paraffin. Histological sections and complete lack of T lymphocytes (5) have were stained with hematoxylin and eosin, recently been found to possess an enhanced methyl green-pyronin, Giemsa solution, Gram bactericidal activity for these organisms during stain and, if required, stains for iron pigment the initial phase of experimentally produced (13). The inflammatory lesions evident in seclisteric infections (2, 3). However, whereas phe- tions of the liver, spleen, and lymph nodes were notypically normal control animals developed a evaluated semiquantitatively as previously recharacteristic short-term listeriosis (7), nude ported (5). In phenotypically normal (nu/+) euthymic mice exhibited signs of a chronic infection (3). Since both observations (high initial bacteri- NMRI mice, the morphology and time course of cidal activity, chronic infection) were based on lesions induced by L. monocytogenes were idenbacteriological studies only (2, 3), these phe- tical to those described by other authors (7, 11). nomena were investigated in the present study Within the first 3 to 4 days p.i., numerous foci of necrosis, densely populated by granulocytes, at the morphological level. Two groups of 50 random-bred female NMRI appeared in the liver. Abscess formation was a mice (specific-pathogen free) were obtained frequent finding. At the same time, extensive from Bomholtgard, Ry, Denmark. The first multiplication of Kupffer cells occurred. From group consisted of congenitally dysthymic nude day 4 on, macrophages and lymphocytes accu(nu/nu) NMRI mice, weighing 16 to 18 g, mulated at the periphery of the hepatic lesions, whereas the second group (control) was com- changing their character from pyogenic to prised of phenotypically normal (nu/+) eu- granulomatous (Fig. 1A). The peak inflammathymic NMRI mice, weighing 22 to 24 g. Both tory response in the liver was observed about 7 groups of mice were kept under conventional days p.i. (Fig. 2). Thereafter, liver lesions rapconditions. Each mouse was intravenously in- idly and completely disappeared. Although fected with a sublethal dose of 1.6 x 103 viable there was considerable variability in the extent 832

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Morphology and time course of experimental listeriosis in nude mice.

Experimental listeriosis in phenotypically normal (nu/+) euthymic NMRI mice has a characteristic morphology and short-term course. In contrast, lister...
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