Influenza virus RNA in the lung and lymphoid tissue of immunologically intact and CD4-depleted mice

Eichelberger, Maryna C.; Wang, Maoliang; Allan, William; Webster, Robert G.; Doherty, Peter C.

doi:10.1099/0022-1317-72-7-1695

Cited by 105 publications

(69 citation statements)

References 12 publications

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“…Flu infects the epithelial cells lining the airways [30], and in mice induces a strong immune response typically resulting in the eradication of virus by day 10 post-infection (unpublished data from our laboratory). Protective immunity is largely due to the action of neutralising antibodies and cytolytic CD8+ T cells, but is paralleled by the accumulation of effector Th1 cells in the MedLN and lung [31,32].…”

Section: Nfat-driven Transcription Is Increased In Cd4+ T Cells Earlymentioning

confidence: 96%

Nuclear factor of activated T (NFAT) cells activity within CD4+ T cells is influenced by activation status and tissue localisation

Harris¹,

Watt²,

MacLenachan³

et al. 2006

Microbes and Infection

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Nuclear factor of activated T (NFAT) cells is a family of transcription factors important for the regulation of cytokine expression by CD4+ T cells. Whilst a number of studies have examined NFAT activity of in vitro generated CD4+ T helper (Th)1 and Th2 cells, regulation of NFAT during in vivo immune responses has yet to be elucidated. We show that NFAT activity in CD4+ T cells peaked at early time-points in the draining mediastinal lymph node of mice infected with influenza A (Flu) or Nippostrongylus brasiliensis (Nb). In contrast, low NFAT transcriptional activity was detected in CD4+ T cells isolated from the lung of either Flu or Nb infected mice, despite a greater proportion of cytokine-producing cells being present at this site. These findings indicate that the activation status and tissue microenvironment of effector CD4+ T cells can determine their requirement for NFAT-mediated transcription.

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Section: Nfat-driven Transcription Is Increased In Cd4+ T Cells Earlymentioning

confidence: 96%

Nuclear factor of activated T (NFAT) cells activity within CD4+ T cells is influenced by activation status and tissue localisation

Harris¹,

Watt²,

MacLenachan³

et al. 2006

Microbes and Infection

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“…This is in sharp contrast to systemic IT, in which the same population is up-regulated ubiquitously throughout both lymphoid and non-lymphoid organs. This is due probably to the fact that influenza is, in most cases, a local infection; virus replication takes place primarily in the respiratory epithelium [26] and induces local cytokine production [39,56,57], whereas during systemic IT cytokines are abundant in circulation. The demonstration that NKG2D is not up-regulated in …”

Section: Cd8mentioning

confidence: 99%

“…S1a for infection model schema), induces a localized immune response which leads to clearance of the virus within 10-14 days [25,26]. This immune response was characterized by significant increases in total numbers of CD8 + T cells within the lung, starting at day 5 [13] (Fig.…”

Section: Phenotype Of Cd8 + T Cells After Primary Influenza Infectionmentioning

confidence: 99%

Influenza infection results in local expansion of memory CD8+ T cells with antigen non-specific phenotype and function

Sckisel

Tietze

Zamora

et al. 2013

Clinical and Experimental Immunology

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Summary Primary viral infections induce activation of CD8+ T cells responsible for effective resistance. We sought to characterize the nature of the CD8 + T cell expansion observed after primary viral infection with influenza. Infection of naive mice with different strains of influenza resulted in the rapid expansion of memory CD8 + T cells exhibiting a unique bystander phenotype with significant up-regulation of natural killer group 2D (NKG2D), but not CD25, on the CD44 high CD8+ T cells, suggesting an antigen non-specific phenotype. We further confirmed the non-specificity of this phenotype on ovalbuminspecific (OT-I) CD8 + T cells, which are not specific to influenza. These nonspecific CD8 + T cells also displayed increased lytic capabilities and were observed primarily in the lung. Thus, influenza infection was shown to induce a rapid, antigen non-specific memory T cell expansion which is restricted to the specific site of inflammation. In contrast, CD8 + T cells of a similar phenotype could be observed in other organs following administration of systemic agonistic anti-CD40 and interleukin-2 immunotherapy, demonstrating that bystander expansion in multiple sites is possible depending on whether the nature of activation is either acute or systemic. Finally, intranasal blockade of NKG2D resulted in a significant increase in viral replication early during the course of infection, suggesting that NKG2D is a critical mediator of anti-influenza responses prior to the initiation of adaptive immunity. These results characterize further the local bystander expansion of tissue-resident, memory CD8 + T cells which, due to their early induction, may play an important NKG2D-mediated, antigen non-specific role during the early stages of viral infection.

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“…Extrapulmonary spread is unusual for laboratory-adapted virus strains such as HKx31 (27,28); however, we consistently detected infectious virus in homogenates prepared from brain (n ϭ 5 out of 5, 4 out of 5, and 5 out of 5 mice in three independent assays), heart (n ϭ 5 out of 5, 5 out of 5, and 5 out of 5 mice in 3 independent assays), and kidneys (n ϭ 4 out of 5 and 3 out of 5 mice in two independent assays) of neutropenic animals infected with HKx31 (Fig. 4C).…”

Section: Virus Replication and Spread In Neutropenic Mice Following Imentioning

confidence: 99%

Neutrophils Ameliorate Lung Injury and the Development of Severe Disease during Influenza Infection

Tate

Deng

Jones

et al. 2009

The Journal of Immunology

283

308

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The clinical response to influenza infection ranges from mild disease to severe pneumonia and it remains unclear whether the inflammatory response to infection is protective or pathogenic. We have defined a novel role for neutrophils in ameliorating lung injury during influenza infection, thereby limiting development of severe disease. Infection of neutrophil-depleted mice with influenza virus HKx31 (H3N2) led to rapid weight loss, pneumonia, and death. Neutropenia was associated with enhanced virus replication in the respiratory tract; however, viral titers were declining at the time of death, leading us to investigate other factors contributing to mortality. In addition to thymic atrophy, lymphopenia, and viremic spread, depletion of neutrophils led to exacerbated pulmonary inflammation, edema, and respiratory dysfunction. Thus, while it is well established that neutrophils contribute to lung injury in a range of pathological conditions, reduced numbers or impaired neutrophil function can facilitate progression of mild influenza to severe clinical disease.

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Influenza virus RNA in the lung and lymphoid tissue of immunologically intact and CD4-depleted mice

Cited by 105 publications

References 12 publications

Nuclear factor of activated T (NFAT) cells activity within CD4+ T cells is influenced by activation status and tissue localisation

Nuclear factor of activated T (NFAT) cells activity within CD4+ T cells is influenced by activation status and tissue localisation

Influenza infection results in local expansion of memory CD8+ T cells with antigen non-specific phenotype and function

Neutrophils Ameliorate Lung Injury and the Development of Severe Disease during Influenza Infection

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