NK cell-derived extracellular granzyme B drives epithelial ulceration during HSV-2 genital infection

Lim, Ying Shiang; Lee, Aisha G.; Jiang, Xiaoping; Scott, Jason; Cofie, Adjoa; Kumar, Sandeep; Kennedy, Dania; Granville, David J.; Shin, Haina

doi:10.1016/j.celrep.2023.112410

Cited by 8 publications

(2 citation statements)

References 92 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Others have found that IL-4 suppresses NK cell cytotoxicity in vitro [ 93 – 95 ]. GZMB also inhibits tissue repair at mucosal surfaces and is being studied as a therapeutic target for wound healing [ 96 , 97 ]. Elevated levels in HbTg compared to Tg animals may be contributing to tissue damage.…”

Section: Discussionmentioning

confidence: 99%

Heligmosomoides bakeri and Toxoplasma gondii co-infection leads to increased mortality associated with changes in immune resistance in the lymphoid compartment and disease pathology

Szabo,

Bowhay,

Forrester

et al. 2024

PLoS ONE

View full text Add to dashboard Cite

Co-infections are a common reality but understanding how the immune system responds in this context is complex and can be unpredictable. Heligmosomoides bakeri (parasitic roundworm, previously Heligmosomoides polygyrus) and Toxoplasma gondii (protozoan parasite) are well studied organisms that stimulate a characteristic Th2 and Th1 response, respectively. Several studies have demonstrated reduced inflammatory cytokine responses in animals co-infected with such organisms. However, while general cytokine signatures have been examined, the impact of the different cytokine producing lymphocytes on parasite control/clearance is not fully understood. We investigated five different lymphocyte populations (NK, NKT, γδ T, CD4+ T and CD8+ T cells), five organs (small intestine, Peyer’s patches, mesenteric lymph nodes, spleen and liver), and 4 cytokines (IFN©, IL-4, IL-10 and IL-13) at two different time points (days 5 and 10 post T. gondii infection). We found that co-infected animals had significantly higher mortality than either single infection. This was accompanied by transient and local changes in parasite loads and cytokine profiles. Despite the early changes in lymphocyte and cytokine profiles, severe intestinal pathology in co-infected mice likely contributed to early mortality due to significant damage by both parasites in the small intestine. Our work demonstrates the importance of taking a broad view during infection research, studying multiple cell types, organs/tissues and time points to link and/or uncouple immunological from pathological findings. Our results provide insights into how co-infection with parasites stimulating different arms of the immune system can lead to drastic changes in infection dynamics.

show abstract

Section: Discussionmentioning

confidence: 99%

Heligmosomoides bakeri and Toxoplasma gondii co-infection leads to increased mortality associated with changes in immune resistance in the lymphoid compartment and disease pathology

Szabo,

Bowhay,

Forrester

et al. 2024

PLoS ONE

View full text Add to dashboard Cite

show abstract

“…This recognition occurs through a variety of mechanisms, including physical contact via either activation or inhibition receptors, or both. In addition, NK cells can become activated through the release of cytokines, such as IL-2, IL-12, IL-15 and IL-18 [ 18 , 19 , 20 ]. When stimulated, these cells secrete a distinct set of cytokines, including IFN-γ (the major cytokine released by NK cells), TNF-α and granulocyte macrophage colony stimulating factor (GM-CSF), as well as chemokines, such as CCL2, CCL3, CCL4 and CCL5 [ 18 , 21 , 22 , 23 ].…”

Section: Introductionmentioning

confidence: 99%

Transcriptome Analysis Identifies the Crosstalk between Dendritic and Natural Killer Cells in Human Cutaneous Leishmaniasis

Nunes,

Tibúrcio,

Bonyek-Silva

et al. 2023

Microorganisms

View full text Add to dashboard Cite

Skin ulcers of cutaneous leishmaniasis (CL) are characterized by a localized inflammatory response mediated by innate and adaptive immune cells, including dendritic cells (DC) and natural killer (NK) cells. Bidirectional interactions between DCs and NK cells contribute to tailor leishmaniasis outcome. Despite advances in the Leishmania biology field in recent decades, the mechanisms involved in DC/NK-mediated control of Leishmania sp. pathogenesis as well as the cellular and molecular players involved in such interaction remain unclear. The present study sought to investigate canonical pathways associated with CL arising from Leishmania braziliensis infection. Initially, two publicly available microarray datasets of skin biopsies from active CL lesions were analyzed, and five pathways were identified using differentially expressed genes. The “Crosstalk between DCs and NK cells” pathway was notable due to a high number of modulated genes. The molecules significantly involved in this pathway were identified, and our findings were validated in newly obtained CL biopsies. We found increased expression of TLR4, TNFRSF1B, IL-15, IL-6, CD40, CCR7, TNF and IFNG, confirming the analysis of publicly available datasets. These findings reveal the “crosstalk between DCs and NK cells” as a potential pathway to be further explored in the pathogenesis of CL, especially the expression of CCR7, which is correlated with lesion development.

show abstract

Vaginal lactobacilli produce anti-inflammatory β-carboline compounds

Glick,

Webber,

Simmons

et al. 2024

Cell Host & Microbe

View full text Add to dashboard Cite

NK cell-derived extracellular granzyme B drives epithelial ulceration during HSV-2 genital infection

Cited by 8 publications

References 92 publications

Heligmosomoides bakeri and Toxoplasma gondii co-infection leads to increased mortality associated with changes in immune resistance in the lymphoid compartment and disease pathology

Heligmosomoides bakeri and Toxoplasma gondii co-infection leads to increased mortality associated with changes in immune resistance in the lymphoid compartment and disease pathology

Transcriptome Analysis Identifies the Crosstalk between Dendritic and Natural Killer Cells in Human Cutaneous Leishmaniasis

Vaginal lactobacilli produce anti-inflammatory β-carboline compounds

Contact Info

Product

Resources

About