Haiying Li1, Tristan I. Evans1, Michelle Connole1, Jacqueline Gillis1

Acute SIV infection induces hypercytotoxicity and massive numerical loss of innate lymphoid cells in the gastrointestinal tract

R. Keith Reeves, Ph.D. HarNew England Primate Research Center Division of vard Medical School Immunology One Pine Hill Drive Southborough, MA 01772 USA Tel: (508)-786-1429 Fax: (508)-624-8172 Mail: [email protected]

Haiying Li1, Tristan I. Evans1, Michelle Connole1, Jacqueline Gillis1, Fay E. Wong1, Yi Yu1, Laura E. Richert-Spuhler2, Nicole R. Klatt2, R. Keith Reeves1 1Division

of Immunology, NEPRC, Harvard Medical School, Southborough, MA 2Department of Pharmaceutics, Washington National Primate Research Center, University of Washington, Seattle, WA



Acute SIV infection induces cytotoxic and multifunctional subpopulations of NKp44+ ILCs

Rapid and tissue-specific depletion of NKp44+ ILCs in the intestinal mucosae during acute SIV infection

% of live munocuclear cells

0

50K

100K 150K 200K 250K

Naive

D6/7

D14

FSC

Chronic

6 4 2 Naive

D6/7

D14

Naive

NKG2A

HLA-DR 100K 150K 200K 250K

0

FSC

1.0

*

**

0.5 0.2 0.1 0.0 Jejunum

F

8

50K

Jejunum and PaLN

C

10

0

0

Chronic

103

CD3

0

103

104

NKp44

105

Tissue: Colon status: Nave

Tissue: Jejunum status: Nave

Tissue: MLN status: Nave

Tissue: Colon status: acute

Tissue: Jejunum status: acute

Tissue: MLN status: acute

MLN

D

Naive D6/7 D14 Chronic

0.3 0.2

Pie Arcs Pie Chart Arc Legend

0.1 0.0

Naive

D6/7

D14

Chronic

C + CD107a F + IFN-

IL-17 I + T + TNF-

G

2 1

Jejunum

105

PaLN

3

0

104

Acute

105

*

**

0

Chronic

% of live munocuclear cells

NKp44+ ILCs NKG2A+ NK cells

2.5 2.0 1.5 1.0 1.0 0.8 0.6 0.4 0.2 0.0

PaLN

0

Colon

B

103 102

0

MLN

A

PaLN

B

4

+

100.0

1 0

Naive

D6/7

D14

Chronic

Figure1. Depletion of NKp44+ ILCs but not NKG2A+ NK cells in intestinal mucosae during SIV infection. (A) Representative gating strategy to identify NKG2A+ NK cells and NKp44+ ILCs among mononuclear cells in mucosal tissues. Frequencies of NKp44+ILCs among mononuclear cells in colon (B), jejunum, PaLN (C), and MLN (D) were compared between naïve, and acutely and chronically SIV-infected rhesus macaques. Frequencies of NKG2A+ NK cells among mononuclear cells in colon (E), jejunum, PaLN (F), and MLN (G) were also evaluated. *, p