Mac-1<sup>+</sup>Cells Are the Predominant Subset in the Early Hepatic Lesions of Mice Infected with<i>Francisella tularensis</i>

Rasmussen, John W.; Cello, Jerónimo; Gil, Horacio; Forestal, Colin A.; Furie, Martha B.; Thanassi, David G.; Benach, Jorge L.

doi:10.1128/iai.00868-06

Cited by 32 publications

(57 citation statements)

References 47 publications

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“…In contrast to Rasmussen et al (25), we observed numerous CD3 ϩ cells within hepatic granulomas of F. tularensis LVSinfected mice as early as day 2 postinfection. As the granulomas grew, CD3 ϩ cells assumed positions near the outer boundaries of these structures, which are similar to the mantles of lymphocytes that form in tuberculous granulomas in mice and guinea pigs (22).…”

Section: Resultscontrasting

confidence: 55%

“…2A). Rasmussen et al (25) have shown that these inflammatory foci contain cells that express surface markers characteristic of macrophages and immature myeloid precursors. The granulomas increased in frequency and size during the first week postinfection ( Fig.…”

Section: Resultsmentioning

confidence: 99%

“…holarctica is a commonly used animal model and is associated with the formation of multifocal hepatic microgranluomas containing CD11b ϩ macrophages and Gr-1 ϩ CD11b ϩ immature myeloid cells followed in time by the appearance of hepatic focal necrosis (25). Neither the process of granuloma formation nor the function of these structures has been systematically studied, and we know little about the determinants of the pathogen or the host that promote their formation or regulate their functions.…”

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confidence: 99%

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NK Cells and Gamma Interferon Coordinate the Formation and Function of Hepatic Granulomas in Mice Infected with theFrancisella tularensisLive Vaccine Strain

Bokhari¹,

Kim²,

Pinson³

et al. 2008

Infect Immun

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Tularemia is a zoonotic infectious disease caused by the facultative intracellular bacterium Francisella tularensis. The initial clinical presentation and dominant features of this condition reflect the mode of transmission and the route of infection. The ulceroglandular form, most frequently acquired from bites of arthropods, is characterized by an initial papular skin lesion that can progress to an eschar or ulcer with regional lymphadenopathy. Inhalation of aerosolized bacteria or secondary hematogenous dissemination of infection to the lungs results in pneumonic tularemia characterized by fever, a broad range in the severity of respiratory symptoms, and a high mortality rate. In the so-called "typhoidal" form of tularemia, patients present with similar systemic symptoms without a clear focus of primary infection. They may show sepsis and rhabdomyolysis with multiorgan system failure, including renal impairment. Following pulmonary and gastrointestinal infection, systemic dissemination of the pathogen leads to the colonization of the liver, where organisms infect both macrophages and hepatocytes (4, 6). At autopsy, the livers of infected human beings often show areas of focal coagulation necrosis throughout the parenchyma of the organ (18).The infection of mice with the live vaccine strain (LVS) of F. tularensis subsp. holarctica is a commonly used animal model and is associated with the formation of multifocal hepatic microgranluomas containing CD11b ϩ macrophages and Gr-1 ϩ

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Section: Resultscontrasting

confidence: 55%

Section: Resultsmentioning

confidence: 99%

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confidence: 99%

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NK Cells and Gamma Interferon Coordinate the Formation and Function of Hepatic Granulomas in Mice Infected with theFrancisella tularensisLive Vaccine Strain

Bokhari¹,

Kim²,

Pinson³

et al. 2008

Infect Immun

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“…Furthermore, a variety of macrophages express GR-1. In fact, one study demonstrates that in the liver, the major cell group infected with F. tularensis is GR-1 ϩ macrophages (33). Thus, making unequivocal conclusions about neutrophils is impossible.…”

Section: Discussionmentioning

confidence: 99%

RespiratoryFrancisella tularensisLive Vaccine Strain Infection Induces Th17 Cells and Prostaglandin E₂, Which Inhibits Generation of Gamma Interferon-Positive T Cells

et al. 2008

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Two key routes of Francisella tularensis infection are through the skin and airway. We wished to understand how the route of inoculation influenced the primary acute adaptive immune response. We show that an intranasal inoculation of the F. tularensis live vaccine strain (LVS) with a 1,000-fold-smaller dose than an intradermal dose results in similar growth kinetics and peak bacterial burdens. In spite of similar bacterial burdens, we demonstrate a difference in the quality, magnitude, and kinetics of the primary acute T-cell response depending on the route of inoculation. Further, we show that prostaglandin E 2 secretion in the lung is responsible for the difference in the gamma interferon (IFN-␥)

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“…The histopathology of hepatic tularemia is characterized by the formation of granuloma-like lesions (13)(14)(15), and the role of gamma interferon (IFN-␥) in their development has been demonstrated (6,36,71). We previously characterized the cellular composition of infected livers using specific cell surface markers showing several types of cells that express the myeloid cell marker CD11b (also known as Mac-1) (55). The largest subpopulation of cells infiltrating the infected livers expressed both Gr-1 and CD11b.…”

Section: Although the Monocytic Cd11bmentioning

confidence: 99%

Phenotypic, Morphological, and Functional Heterogeneity of Splenic Immature Myeloid Cells in the Host Response to Tularemia

et al. 2012

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ABSTRACTRecent studies have linked accumulation of the Gr-1+CD11b+cell phenotype with functional immunosuppression in diverse pathological conditions, including bacterial and parasitic infections and cancer. Gr-1+CD11b+cells were the largest population of cells present in the spleens of mice infected with sublethal doses of theFrancisella tularensislive vaccine strain (LVS). In contrast, the number of T cells present in the spleens of these mice did not increase during early infection. There was a significant delay in the kinetics of accumulation of Gr-1+CD11b+cells in the spleens of B-cell-deficient mice, indicating that B cells play a role in recruitment and maintenance of this population in the spleens of mice infected withF. tularensis. The splenic Gr-1+CD11b+cells in tularemia were a heterogeneous population that could be further subdivided into monocytic (mononuclear) and granulocytic (polymorphonuclear) cells using the Ly6C and Ly6G markers and differentiated into antigen-presenting cells followingex vivoculture. Monocytic, CD11b+Ly6ChiLy6G−cells but not granulocytic, CD11b+Ly6CintLy6G+cells purified from the spleens of mice infected withF. tularensissuppressed polyclonal T-cell proliferation via a nitric oxide-dependent pathway. Although the monocytic, CD11b+Ly6ChiLy6G−cells were able to suppress the proliferation of T cells, the large presence of Gr-1+CD11b+cells in mice that survivedF. tularensisinfection also suggests a potential role for these cells in the protective host response to tularemia.

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Mac-1⁺Cells Are the Predominant Subset in the Early Hepatic Lesions of Mice Infected withFrancisella tularensis

Cited by 32 publications

References 47 publications

NK Cells and Gamma Interferon Coordinate the Formation and Function of Hepatic Granulomas in Mice Infected with theFrancisella tularensisLive Vaccine Strain

NK Cells and Gamma Interferon Coordinate the Formation and Function of Hepatic Granulomas in Mice Infected with theFrancisella tularensisLive Vaccine Strain

RespiratoryFrancisella tularensisLive Vaccine Strain Infection Induces Th17 Cells and Prostaglandin E₂, Which Inhibits Generation of Gamma Interferon-Positive T Cells

Phenotypic, Morphological, and Functional Heterogeneity of Splenic Immature Myeloid Cells in the Host Response to Tularemia

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Mac-1+Cells Are the Predominant Subset in the Early Hepatic Lesions of Mice Infected withFrancisella tularensis

Cited by 32 publications

References 47 publications

NK Cells and Gamma Interferon Coordinate the Formation and Function of Hepatic Granulomas in Mice Infected with theFrancisella tularensisLive Vaccine Strain

NK Cells and Gamma Interferon Coordinate the Formation and Function of Hepatic Granulomas in Mice Infected with theFrancisella tularensisLive Vaccine Strain

RespiratoryFrancisella tularensisLive Vaccine Strain Infection Induces Th17 Cells and Prostaglandin E2, Which Inhibits Generation of Gamma Interferon-Positive T Cells

Phenotypic, Morphological, and Functional Heterogeneity of Splenic Immature Myeloid Cells in the Host Response to Tularemia

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Mac-1⁺Cells Are the Predominant Subset in the Early Hepatic Lesions of Mice Infected withFrancisella tularensis

RespiratoryFrancisella tularensisLive Vaccine Strain Infection Induces Th17 Cells and Prostaglandin E₂, Which Inhibits Generation of Gamma Interferon-Positive T Cells