{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T14:01:47Z","timestamp":1785420107946,"version":"3.56.0"},"reference-count":81,"publisher":"American Society for Microbiology","issue":"4","license":[{"start":{"date-parts":[[2026,4,8]],"date-time":"2026-04-08T00:00:00Z","timestamp":1775606400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,4,8]],"date-time":"2026-04-08T00:00:00Z","timestamp":1775606400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R37 AI072683, R01 AI139072, R01 AI167857"],"award-info":[{"award-number":["R37 AI072683, R01 AI139072, R01 AI167857"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["mBio"],"published-print":{"date-parts":[[2026,4,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      <jats:italic toggle=\"yes\">Anaplasma phagocytophilum<\/jats:italic>\n                      is an obligate intracellular bacterium that invades neutrophils to cause the potentially severe infection, human granulocytic anaplasmosis. The\n                      <jats:italic toggle=\"yes\">A. phagocytophilum<\/jats:italic>\n                      invasin-host cell receptor interactions that facilitate bacterial uptake and hence disease are incompletely defined. Here, we show that EPHNCH_1611, which we refer to as\n                      <jats:italic toggle=\"yes\">A. phagocytophilum<\/jats:italic>\n                      invasion protein B (AipB), mediates bacterial entry but not adhesion. The AipB host cell-interacting domain was narrowed down to amino acids 109 to 129 and is conserved among\n                      <jats:italic toggle=\"yes\">Anaplasma<\/jats:italic>\n                      and\n                      <jats:italic toggle=\"yes\">Ehrlichia<\/jats:italic>\n                      species. AipB\n                      <jats:sub>109-123<\/jats:sub>\n                      antisera reduced\n                      <jats:italic toggle=\"yes\">A. phagocytophilum<\/jats:italic>\n                      infection of host cells by 28%. Combining anti-AipB\n                      <jats:sub>109-123<\/jats:sub>\n                      with antisera specific for the receptor binding domains of previously identified invasins AipA, Asp14, and OmpA reduced infection by 93%, suggesting a synergistic relationship among these surface proteins. Immunizing mice against AipB\n                      <jats:sub>109-123<\/jats:sub>\n                      alone yielded partial protection from\n                      <jats:italic toggle=\"yes\">A. phagocytophilum<\/jats:italic>\n                      challenge that rivaled the protection achieved by immunizing against it together with other invasin binding domains. A yeast two-hybrid screen identified the N-terminal domain of CD18, the \u03b22 integrin \u03b2-subunit found on the neutrophil surface, as an AipB binding partner. The interaction was validated by co-immunoprecipitation. siRNA knockdown of CD18 reduced permissiveness to\n                      <jats:italic toggle=\"yes\">A. phagocytophilum<\/jats:italic>\n                      infection. Antibodies targeting the CD18 N-terminus inhibited\n                      <jats:italic toggle=\"yes\">A. phagocytophilum<\/jats:italic>\n                      infection of, but not adherence to, HL-60 cells and human neutrophils. These results demonstrate that the AipB-CD18 interaction is critical for\n                      <jats:italic toggle=\"yes\">A. phagocytophilum<\/jats:italic>\n                      infection\n                      <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                      and\n                      <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                      , further dissecting the multifaceted mechanism by which\n                      <jats:italic toggle=\"yes\">A. phagocytophilum<\/jats:italic>\n                      invades host cells.\n                    <\/jats:p>\n                    <jats:sec>\n                      <jats:title>IMPORTANCE<\/jats:title>\n                      <jats:p>\n                        <jats:italic toggle=\"yes\">Anaplasma phagocytophilum<\/jats:italic>\n                        causes human granulocytic anaplasmosis, an emerging tick-borne infection for which there is no vaccine and limited treatments. Although\n                        <jats:italic toggle=\"yes\">A. phagocytophilum<\/jats:italic>\n                        absolutely relies on invading host neutrophils to survive and cause disease, the microbe-host cell interactions that predicate infection are inadequately defined. We found that the bacterium uses its outer surface protein AipB to engage CD18 as a critical invasion step. An AipB peptide that is conserved among its homologs in other\n                        <jats:italic toggle=\"yes\">Anaplasmataceae<\/jats:italic>\n                        pathogens is responsible for binding CD18 and can be targeted by antibody to inhibit infection\n                        <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                        and\n                        <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                        . However, blocking of\n                        <jats:italic toggle=\"yes\">A. phagocytophilum<\/jats:italic>\n                        infection is most effectively achieved by targeting this AipB peptide together with the functional domains of other invasins. AipB is the first rickettsial invasin identified to interact with a \u03b22 integrin, is key for pathogenesis, and could be targeted to protect against diseases caused by\n                        <jats:italic toggle=\"yes\">A. phagocytophilum<\/jats:italic>\n                        and other\n                        <jats:italic toggle=\"yes\">Anaplasmataceae<\/jats:italic>\n                        bacteria.\n                      <\/jats:p>\n                    <\/jats:sec>\n                  <\/jats:sec>","DOI":"10.1128\/mbio.03853-25","type":"journal-article","created":{"date-parts":[[2026,2,24]],"date-time":"2026-02-24T14:01:28Z","timestamp":1771941688000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":0,"title":["<i>Anaplasma phagocytophilum<\/i>\n                    invasin AipB interacts with the \u03b22 integrin \u03b2-subunit CD18 to orchestrate infection"],"prefix":"10.1128","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6060-6918","authenticated-orcid":false,"given":"Mary Clark H.","family":"Lind","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/057xmsr27","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Microbiology and Immunology, School of Medicine, Virginia Commonwealth University Medical Center","place":["Richmond, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Waheeda A.","family":"Naimi","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/057xmsr27","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Microbiology and Immunology, School of Medicine, Virginia Commonwealth University Medical Center","place":["Richmond, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason 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