# Host Innate Immune Responses to Acinetobacter baumannii Infection

**Authors:** Wangxue Chen

PMC · DOI: 10.3389/fcimb.2020.00486 · 2020-09-14

## TL;DR

This paper reviews how the body's innate immune system responds to Acinetobacter baumannii infection and highlights the need for new treatments.

## Contribution

The paper identifies gaps in understanding host immune responses to A. baumannii and emphasizes the need for novel therapeutic targets.

## Key findings

- A. baumannii triggers inflammatory cytokine and chemokine responses.
- Innate immune effectors like neutrophils and macrophages are recruited to fight the infection.
- Current knowledge is insufficient for developing effective vaccines and immunotherapeutics.

## Abstract

Acinetobacter baumannii has emerged as a major threat to global public health and is one of the key human pathogens in healthcare (nosocomial and community-acquired)-associated infections. Moreover, A. baumannii rapidly develops resistance to multiple antibiotics and is now globally regarded as a serious multidrug resistant pathogen. There is an urgent need to develop novel vaccines and immunotherapeutics as alternatives to antibiotics for clinical management of A. baumannii infection. However, our knowledge of host immune responses to A. baumannii infection and the identification of novel therapeutic targets are significantly lacking. This review highlights the recent advances and critical gaps in our understanding how A. baumannii interacts with the host innate pattern-recognition receptors, induces a cascade of inflammatory cytokine and chemokine responses, and recruits innate immune effectors (such as neutrophils and macrophages) to the site of infection for effective control of the infection. Such knowledge will facilitate the identification of new targets for the design and development of effective therapeutics and vaccines to fight this emerging threat.

## Linked entities

- **Species:** Acinetobacter baumannii (taxon 470)

## Full-text entities

- **Genes:** Tlr2 (toll-like receptor 2) [NCBI Gene 310553], Ifng (interferon gamma) [NCBI Gene 25712] {aka IFNG2, If2f}, Cxcl15 (C-X-C motif chemokine ligand 15) [NCBI Gene 20309] {aka Il8, Scyb15, lungkine, weche}, Tlr9 (toll-like receptor 9) [NCBI Gene 81897], Ccl5 (C-C motif chemokine ligand 5) [NCBI Gene 20304] {aka MuRantes, RANTES, SISd, Scya5, TCP228}, Il12b (interleukin 12b) [NCBI Gene 16160] {aka Il-12b, Il-12p40, Il12p40, p40}, Arhgdig (Rho GDP dissociation inhibitor gamma) [NCBI Gene 14570] {aka Gdi5, RIP2, Rho-GDI-3, Rho-GDI2}, Nlrc4 (NLR family, CARD domain containing 4) [NCBI Gene 268973] {aka 9530011P19Rik, CLAN, CLAN1, CLANA, CLANB, CLANC}, Nos2 (nitric oxide synthase 2) [NCBI Gene 24599] {aka Nos2a, iNos}, Tnf (tumor necrosis factor) [NCBI Gene 21926] {aka DIF, TNF-a, TNF-alpha, TNFSF2, TNFalpha, Tnfa}, Igha (immunoglobulin heavy constant alpha) [NCBI Gene 238447] {aka IgA, Igh-2}, Pycard (PYD and CARD domain containing) [NCBI Gene 282817] {aka Asc}, TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}, Tlr2 (toll-like receptor 2) [NCBI Gene 24088] {aka Ly105}, Il23a (interleukin 23, alpha subunit p19) [NCBI Gene 83430] {aka IL-23, p19}, Cd14 (CD14 antigen) [NCBI Gene 12475], Nfkb1 (nuclear factor of kappa light polypeptide gene enhancer in B cells 1, p105) [NCBI Gene 18033] {aka NF-KB1, NF-kappaB, NF-kappaB1, p105, p50, p50/p105}, Creb1 (cAMP responsive element binding protein 1) [NCBI Gene 12912] {aka 2310001E10Rik, 3526402H21Rik, Creb, Creb-1}, Stat3 (signal transducer and activator of transcription 3) [NCBI Gene 20848] {aka 1110034C02Rik, Aprf}, Il10 (interleukin 10) [NCBI Gene 16153] {aka CSIF, If2a, Il-10}, Lpo (lactoperoxidase) [NCBI Gene 287610], Ifng (interferon gamma) [NCBI Gene 15978] {aka IFN-g, If2f, Ifg}, Tlr9 (toll-like receptor 9) [NCBI Gene 338457], Il1 (interleukin 1 complex) [NCBI Gene 111343] {aka Il-1}, Il4 (interleukin 4) [NCBI Gene 16189] {aka BSF-1, Il-4}, Il17a (interleukin 17A) [NCBI Gene 16171] {aka Ctla-8, Ctla8, IL-17, IL-17A, Il17}, Cd4 (CD4 antigen) [NCBI Gene 12504] {aka L3T4, Ly-4}, Il33 (interleukin 33) [NCBI Gene 77125] {aka 9230117N10Rik, Il-33, Il1f11, NF-HEV}, Adam17 (a disintegrin and metallopeptidase domain 17) [NCBI Gene 11491] {aka CD156b, Tace}, MAPK1 (mitogen-activated protein kinase 1) [NCBI Gene 5594] {aka ERK, ERK-2, ERK2, ERT1, MAPK2, NS13}, CFH (complement factor H) [NCBI Gene 3075] {aka AHUS1, AMBP1, ARMD4, ARMS1, CFHL3, FH}, Cxcl2 (C-X-C motif chemokine ligand 2) [NCBI Gene 20310] {aka CINC-2a, GROb, Gro2, MIP-2, MIP-2a, Mgsa-b}, Ager (advanced glycosylation end product-specific receptor) [NCBI Gene 11596] {aka RAGE}, Tlr4 (toll-like receptor 4) [NCBI Gene 21898] {aka Lps, Ly87, Ran/M1, Rasl2-8}, Defb2 (defensin beta 2) [NCBI Gene 13215] {aka BD-2}, Mpo (myeloperoxidase) [NCBI Gene 17523] {aka mKIAA4033}, Nos2 (nitric oxide synthase 2, inducible) [NCBI Gene 18126] {aka MAC-NOS, NOS-II, Nos-2, Nos2a, i-NOS, iNOS}, Egfr (epidermal growth factor receptor) [NCBI Gene 13649] {aka 9030024J15Rik, Erbb, Errb1, Errp, Wa5, wa-2}, C3 (complement component 3) [NCBI Gene 12266] {aka ASP, HSE-MSF, Plp}, NFKB1 (nuclear factor kappa B subunit 1) [NCBI Gene 4790] {aka CVID12, EBP-1, KBF1, NF-kB, NF-kB1, NF-kappa-B1}, Il6 (interleukin 6) [NCBI Gene 16193] {aka Il-6}, Cybb (cytochrome b-245, beta polypeptide) [NCBI Gene 13058] {aka CGD91-phox, Cgd, Cyd, Nox2, gp91-1, gp91phox}, Il1b (interleukin 1 beta) [NCBI Gene 16176] {aka IL-1beta, Il-1b}, Cxcl1 (C-X-C motif chemokine ligand 1) [NCBI Gene 81503] {aka CINC-1, Gro1}, NLRP3 (NLR family pyrin domain containing 3) [NCBI Gene 114548] {aka AGTAVPRL, AII, AVP, C1orf7, CIAS1, CLR1.1}, Il18 (interleukin 18) [NCBI Gene 16173] {aka Igif, Il-18}, Fcgr2b (Fc receptor, IgG, low affinity IIb) [NCBI Gene 14130] {aka CD32, F630109E10Rik, Fc[g]RII, FcgRII, Fcgr2, Fcgr2a}, CXCL8 (C-X-C motif chemokine ligand 8) [NCBI Gene 3576] {aka GCP-1, GCP1, IL8, LECT, LUCT, LYNAP}, TLR9 (toll like receptor 9) [NCBI Gene 54106] {aka CD289}, Nod2 (nucleotide-binding oligomerization domain containing 2) [NCBI Gene 257632] {aka ACUG, BLAU, CD, Card15, F830032C23Rik, IBD1}, Il17a (interleukin 17A) [NCBI Gene 301289] {aka CTLA-8, IL-17, IL-17A, Il17}, Tnf (tumor necrosis factor) [NCBI Gene 24835] {aka RATTNF, TNF-alpha, Tnfa}, Casp1 (caspase 1) [NCBI Gene 12362] {aka ICE, Il1bc}, Mapk14 (mitogen-activated protein kinase 14) [NCBI Gene 26416] {aka CSBP2, Crk1, Csbp1, Mxi2, PRKM14, PRKM15}, Nlrp3 (NLR family, pyrin domain containing 3) [NCBI Gene 216799] {aka AGTAVPRL, AII/AVP, Cias1, FCAS, FCU, MWS}, Il10 (interleukin 10) [NCBI Gene 25325] {aka IL10X, If2a}, Ltf (lactotransferrin) [NCBI Gene 17002] {aka Csp82, Lf, MMS10R, Ms10r}, Tusc2 (tumor suppressor 2, mitochondrial calcium regulator) [NCBI Gene 80385] {aka 1190001E22Rik, Fus1, Lgcc, PAP, Pdap2}, Il2 (interleukin 2) [NCBI Gene 16183] {aka Il-2}, Nod1 (nucleotide-binding oligomerization domain containing 1) [NCBI Gene 107607] {aka C230079P11, Card4, F830007N14Rik, Nlrc1, mNod1}
- **Diseases:** Acinetobacter baumannii Infection (MESH:D000151), bacterial (MESH:D001424), nosocomial (MESH:D003428), diabetic (MESH:D003920), pneumonia (MESH:D011014), necrosis (MESH:D009336), bacteremia (MESH:D016470), cancer (MESH:D009369), sepsis (MESH:D018805), viral infections (MESH:D014777), pulmonary tissue damage (MESH:D055370), burn (MESH:D002056), blood and urinary tract infections (MESH:D014552), bacteria (MESH:C000719206), meningitis (MESH:D008580), acute inflammation (MESH:D007249), cytotoxic (MESH:D064420), NHS (MESH:D012713), proinflammatory cytokines (MESH:D000080424), wound- (MESH:D014947), lung infection (MESH:D012141), skin and soft tissue infections (MESH:D018461), neutropenic (MESH:D044504), NETs (MESH:C536657), A. baumannii infection (MESH:D007239), bacteraemia (MESH:C531821), neutropenia (MESH:D009503), gastrointestinal bacterial (MESH:D005767), damage (MESH:D020263), lung (MESH:D008171), neutrophil dysfunction (MESH:C564942)
- **Species:** Rattus norvegicus (brown rat, species) [taxon 10116], Pseudomonas aeruginosa PAO1 (strain) [taxon 208964], Homo sapiens (human, species) [taxon 9606], Acinetobacter junii (species) [taxon 40215], Drosophila melanogaster (fruit fly, species) [taxon 7227], Bacteria Latreille et al. 1825 (Bacteria stick insect, genus) [taxon 629395], Acinetobacter baumannii (species) [taxon 470], Mus musculus (house mouse, species) [taxon 10090], Pseudomonas aeruginosa (species) [taxon 287]
- **Mutations:** T1237C, D299G, T399I
- **Cell lines:** S2 — Drosophila melanogaster (Fruit fly), Spontaneously immortalized cell line (CVCL_Z232), RAW264.7 — Mus musculus (Mouse), Mouse leukemia, Cancer cell line (CVCL_0493), HEK-293 — Homo sapiens (Human), Transformed cell line (CVCL_0045), LAD2 — Homo sapiens (Human), Factor-dependent cell line (CVCL_0387), THP-1 — Homo sapiens (Human), Childhood acute monocytic leukemia, Cancer cell line (CVCL_0006), HEp-2 — Homo sapiens (Human), Human papillomavirus-related endocervical adenocarcinoma, Cancer cell line (CVCL_1906), C57BL/6 — Mus musculus (Mouse), Transformed cell line (CVCL_C0MU), A549 — Homo sapiens (Human), Lung adenocarcinoma, Cancer cell line (CVCL_0023)

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Source: https://tomesphere.com/paper/PMC7521131