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Functional perturbation of classical natural killer and innate lymphoid cells in the oral mucosa during SIV infection.

Li H, Reeves RK - Front Immunol (2013)

Bottom Line: Also in contrast to what we have previously found in gut tissues of SIV-infected macaques, we found no reduction in NK cells during chronic SIV infection, but rather an expansion of ILCs in oral-draining lymph nodes and tonsils.These data suggest that the lentivirus-induced depletion of the NK cell/ILC compartment in the gut may be absent in the oral mucosa, but the inherent differences and SIV-induced alterations are likely to have significant impact on preventing oral opportunistic infections in lentiviral disease.Furthermore, these data extend our understanding of the oral innate immune system in general and could aid future studies evaluating the regulation of both normal oral flora and limiting transmission of oral mucosal pathogens.

View Article: PubMed Central - PubMed

Affiliation: Division of Immunology, New England Primate Research Center, Harvard Medical School, One Pine Hill Drive Southborough, MA, USA.

ABSTRACT
Despite the fact that the majority of human pathogens are transmitted across mucosal surfaces, including the oral mucosae, oral immunity is poorly understood. Furthermore, because the normal flora of the oral cavity is vast and significantly diverse, host immunity must balance a complex system of tolerance and pathogen recognition. Due to the rapid recognition and response to pathogens, the innate immune system, including natural killer (NK) cells, likely plays a critical role in mediating this balance. Because logistical and ethical restraints limit access to significant quantities of human mucosal tissues, non-human primate models offer one of the best opportunities to study mucosal NK cells. In this study we have identified both classical NK cells, as well as innate lymphoid cells (ILCs) in tonsillar and buccal tissues and oral-draining lymph nodes. Identified by mutually exclusive expression of NKG2A and NKp44, NK cells, and ILCs in the oral mucosa are generally phenotypically and functionally analogous to their gut counterparts. NKG2A(+) NK cells were more cytotoxic while NKp44(+) ILCs produced copious amounts of IL-17 and TNF-α. However, in contrast to gut, oral NK cells and ILCs both produced large quantities of IFN-γ and the beta-chemokine, MIP-1β. Also in contrast to what we have previously found in gut tissues of SIV-infected macaques, we found no reduction in NK cells during chronic SIV infection, but rather an expansion of ILCs in oral-draining lymph nodes and tonsils. These data suggest that the lentivirus-induced depletion of the NK cell/ILC compartment in the gut may be absent in the oral mucosa, but the inherent differences and SIV-induced alterations are likely to have significant impact on preventing oral opportunistic infections in lentiviral disease. Furthermore, these data extend our understanding of the oral innate immune system in general and could aid future studies evaluating the regulation of both normal oral flora and limiting transmission of oral mucosal pathogens.

No MeSH data available.


Related in: MedlinePlus

Classical NK cells and ILCs in the oral mucosa have distinct functional profiles. Representative flow cytometry plots depicting CD107a and intracellular cytokine responses in NK cells and ILCs in the oral mucosa following mitogen stimulation. ICS profiles are representative of a total of 13 animals.
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Figure 3: Classical NK cells and ILCs in the oral mucosa have distinct functional profiles. Representative flow cytometry plots depicting CD107a and intracellular cytokine responses in NK cells and ILCs in the oral mucosa following mitogen stimulation. ICS profiles are representative of a total of 13 animals.

Mentions: We next evaluated the functionality of classical NKG2A+ NK cells and NKp44+ ILCs using a four-function ICS assay (Reeves et al., 2010). Due to limited quantities of cells isolated from oral tissues we only addressed functionality using OLN. Following mitogen stimulation NKG2A+ NK cells secreted no IL-17 and little TNF-α, but produced significant amounts of IFN-γ and MIP-1β (Figure 3). In contrast, ILCs secreted the regulatory cytokines IL-17 and TNF-α as well as IFN-γ and MIP-1β. The functional profile of ILCs in OLN was similar to that of GI ILCs with one notable exception—ILCs in the gut do not generally produce IFN-γ (Reeves et al., 2011). In response to stimulation, classical NK cells upregulated a surrogate marker for degranulation, CD107a, whereas ILCs expressed only very low levels. This indicated not surprisingly that ILCs were generally non-cytotoxic. Interestingly, both NK cells and ILCs were robust producers of MIP-1β, which could contribute to blocking of SIV infection and replication in the oral mucosa.


Functional perturbation of classical natural killer and innate lymphoid cells in the oral mucosa during SIV infection.

Li H, Reeves RK - Front Immunol (2013)

Classical NK cells and ILCs in the oral mucosa have distinct functional profiles. Representative flow cytometry plots depicting CD107a and intracellular cytokine responses in NK cells and ILCs in the oral mucosa following mitogen stimulation. ICS profiles are representative of a total of 13 animals.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3539714&req=5

Figure 3: Classical NK cells and ILCs in the oral mucosa have distinct functional profiles. Representative flow cytometry plots depicting CD107a and intracellular cytokine responses in NK cells and ILCs in the oral mucosa following mitogen stimulation. ICS profiles are representative of a total of 13 animals.
Mentions: We next evaluated the functionality of classical NKG2A+ NK cells and NKp44+ ILCs using a four-function ICS assay (Reeves et al., 2010). Due to limited quantities of cells isolated from oral tissues we only addressed functionality using OLN. Following mitogen stimulation NKG2A+ NK cells secreted no IL-17 and little TNF-α, but produced significant amounts of IFN-γ and MIP-1β (Figure 3). In contrast, ILCs secreted the regulatory cytokines IL-17 and TNF-α as well as IFN-γ and MIP-1β. The functional profile of ILCs in OLN was similar to that of GI ILCs with one notable exception—ILCs in the gut do not generally produce IFN-γ (Reeves et al., 2011). In response to stimulation, classical NK cells upregulated a surrogate marker for degranulation, CD107a, whereas ILCs expressed only very low levels. This indicated not surprisingly that ILCs were generally non-cytotoxic. Interestingly, both NK cells and ILCs were robust producers of MIP-1β, which could contribute to blocking of SIV infection and replication in the oral mucosa.

Bottom Line: Also in contrast to what we have previously found in gut tissues of SIV-infected macaques, we found no reduction in NK cells during chronic SIV infection, but rather an expansion of ILCs in oral-draining lymph nodes and tonsils.These data suggest that the lentivirus-induced depletion of the NK cell/ILC compartment in the gut may be absent in the oral mucosa, but the inherent differences and SIV-induced alterations are likely to have significant impact on preventing oral opportunistic infections in lentiviral disease.Furthermore, these data extend our understanding of the oral innate immune system in general and could aid future studies evaluating the regulation of both normal oral flora and limiting transmission of oral mucosal pathogens.

View Article: PubMed Central - PubMed

Affiliation: Division of Immunology, New England Primate Research Center, Harvard Medical School, One Pine Hill Drive Southborough, MA, USA.

ABSTRACT
Despite the fact that the majority of human pathogens are transmitted across mucosal surfaces, including the oral mucosae, oral immunity is poorly understood. Furthermore, because the normal flora of the oral cavity is vast and significantly diverse, host immunity must balance a complex system of tolerance and pathogen recognition. Due to the rapid recognition and response to pathogens, the innate immune system, including natural killer (NK) cells, likely plays a critical role in mediating this balance. Because logistical and ethical restraints limit access to significant quantities of human mucosal tissues, non-human primate models offer one of the best opportunities to study mucosal NK cells. In this study we have identified both classical NK cells, as well as innate lymphoid cells (ILCs) in tonsillar and buccal tissues and oral-draining lymph nodes. Identified by mutually exclusive expression of NKG2A and NKp44, NK cells, and ILCs in the oral mucosa are generally phenotypically and functionally analogous to their gut counterparts. NKG2A(+) NK cells were more cytotoxic while NKp44(+) ILCs produced copious amounts of IL-17 and TNF-α. However, in contrast to gut, oral NK cells and ILCs both produced large quantities of IFN-γ and the beta-chemokine, MIP-1β. Also in contrast to what we have previously found in gut tissues of SIV-infected macaques, we found no reduction in NK cells during chronic SIV infection, but rather an expansion of ILCs in oral-draining lymph nodes and tonsils. These data suggest that the lentivirus-induced depletion of the NK cell/ILC compartment in the gut may be absent in the oral mucosa, but the inherent differences and SIV-induced alterations are likely to have significant impact on preventing oral opportunistic infections in lentiviral disease. Furthermore, these data extend our understanding of the oral innate immune system in general and could aid future studies evaluating the regulation of both normal oral flora and limiting transmission of oral mucosal pathogens.

No MeSH data available.


Related in: MedlinePlus