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Correspondence |
Research Center Borstel Borstel, Germany
To the Editor-in-Chief:
It has been reported that T cells are involved in the process of granuloma formation and may be necessary to induce the formation of granulomas.1 However, in an issue of The American Journal of Pathology, North and Izzo showed the formation of granulomas in severe combined immunodeficient (SCID) mice, which are not able to generate efficient T and B cells, after infection with Bacillus Calmette-Guerin (BCG).2 These granulomas were found in spleen and liver. Moreover, the authors described a deficiency of these SCID mice to form granulomas in the lungs after inoculation with BCG.2 In an attempt to establish a granuloma model to analyze the process of granuloma formation, we intravenously inoculated SCID mice with BCG (strain Connaught) for means of control and examined the animals histomorphologically after 30 days.
Three 10- to 12-week-old female C.B.-17scid/scid mice were housed in filter-top cages in an incubator with a constant horizontal flow of filtered air and supplied with food and water ad libitum. The mice were inoculated intravenously with BCG (108 CFU per animal; courtesy of E. Richter, National Reference Center for Mycobacteria, Borstel, Germany). The mice were sacrificed 28 to 30 days after inoculation, and the organs were kept in buffered formaldehyde solution (4% vol/vol). The tissue was paraffin-embedded, sliced, and hematoxylin-and-eosin-stained. Visualization of BCG in the tissues was performed by Ziehl-Neelsen staining.
With regard to the formation of granulomas in spleen and liver, we
reproduced the results obtained in the study of North and
Izzo.2
Furthermore, in accordance with previous results,
we found isolated alveolar macrophages infected with BCG in the lungs
of these mice.2
However, we also observed the generation
of well formed granulomas in the lungs of these mice. These granulomas
were not just aggregations of alveolar macrophages, but were
morphologically comparable to the granulomas found in spleen and liver
(Figure 1a)
. Inside the pulmonary
granulomas, acid fast bacilli were detected by Ziehl-Neelsen staining
(Figure 1b)
and identified as mycobacteria from the Mycobacterium
tuberculosis complex by means of polymerase chain reaction
targeting mycobacterial 16S rDNA.3
This demonstrates that,
upon infection with BCG, SCID mice can produce pulmonary granulomas.
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release, the delivery of
interferon-
(IFN-) is an important prerequisite for granuloma
formation and the eradication of the bacteria.4,5
In
immunocompetent mice the most important source of IFN- is Th1 cells.
In a recent publication, it was demonstrated that the development of
T-cell-independent granuloma is reliant on the induction of IFN-
release by natural killer (NK) cells.6
The induction of
NK-cell IFN- release is dependent on the release of
interleukin-12 and -10 by macrophages.7,8
In a
model of Pneumocystis carinii infection, it was demonstrated
that although alveolar macrophages are able to stimulate NK cells to
release IFN-, they are inferior compared to splenic
macrophages.8
North and Izzo used the BCG strain Pasteur, so it can be
speculated that there might be strain-specific differences in the
induction of IFN--inducing factors by macrophages in the lung,
liver, and spleen, since the number of bacteria injected and the time
spans of infection have been comparable.
Our experiments demonstrate that the presence of T cells is not mandatory for the generation of pulmonary granulomas in SCID mice. We conclude that SCID mice infected with BCG are capable of generating granulomas in the lungs.
References
This article has been cited by other articles:
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  A. Stein, C. Louveau, H. Lepidi, F. Ricci, P. Baylac, B. Davoust, and D. Raoult Q Fever Pneumonia: Virulence of Coxiella burnetii Pathovars in a Murine Model of Aerosol Infection Infect. Immun., April 1, 2005; 73(4): 2469 - 2477. [Abstract] [Full Text] [PDF]
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